Back to resultsLong-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
Primary Purpose
Hypertension, Pulmonary
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ambrisentan
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension, Pulmonary focused on measuring pulmonary arterial hypertension, pediatrics
Eligibility Criteria
Inclusion Criteria:
Have participated in and complied, to the best of their ability, with the protocol for AMB112529 and have met one of the following:
- Completed the Week 24 visit in AMB112529;
- Required additional targeted treatment for PAH due to inadequate response to the current treatment or worsening of their clinical condition prior to week 24 in AMB112529;
- Required reduction in dose of baseline targeted treatment for PAH after ambrisentan was added to the treatment regimen;
- In the opinion of the investigator, continued treatment with ambrisentan is warranted.
A female is eligible to participate in this study, as assessed by the investigator, if she is of:
- Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,
- Child-bearing potential - has a negative pregnancy test and is not lactating and, if sexually active, agrees to continue to use 2 reliable methods of contraception until study completion and for at least 30 days following the last dose of study drug (reliable methods of contraception are listed in Appendix 2).
- Subject or subject's legal guardian is able and willing to give written informed consent. As part of the consent, female subjects of childbearing potential will be informed of the risk of teratogenicity and will need to be counselled in a developmentally appropriate manner on the importance of pregnancy prevention; and male subjects will need to be informed of potential risk of testicular tubular atrophy and aspermia.
Exclusion Criteria:
- Subjects who were withdrawn from ambrisentan in Study AMB112529;
- Subjects who did not comply with the protocol in Study AMB112529;
- Female subjects who are pregnant or breastfeeding;
- Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min assessed within the previous 45 days) at the point of transition from Study AMB112529 into this study;
- Subject with clinically significant fluid retention in the opinion of the investigator;
- Subject with clinically significant anaemia in the opinion of the investigator;
- Subjects who are to enter another clinical trial or be treated with another investigational product after exiting Study AMB112529.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ambrisentan
Arm Description
Open label, flexible dosing from 2.5 mg to 10 mg (not to exceed 0.25 mg/kg) per day
Outcomes
Primary Outcome Measures
Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)
AE was defined as any untoward medical occurrence in participant or clinical investigation participant,temporally associated with use of medicinal product, whether or not considered related to medicinal product.SAE was 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 congenital anomaly or birth defect, important medical events that may not immediately life threatening or result in death or hospitalization but may jeopardize participant or may require medical or surgical intervention as per medical or scientific judgement or associated with drug-induced liver injury.TEAE is any event that was not present prior to initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs which were not serious TEAEs were considered as non serious TEAEs.
Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin
Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALT, AST, GGT, total bilirubin. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN)
Blood samples were collected from participants for analysis of following clinical chemistry parameters: Calcium, chloride, CO2 content, glucose, potassium, magnesium, sodium, phosphorus inorganic, and BUN. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)
Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALP, CK, LDH. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid
Blood samples were collected from participants for analysis of following clinical chemistry parameters: Creatinine, uric acid. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Chemistry Parameters: Albumin, Total Protein
Blood samples were collected from participants for analysis of following clinical chemistry parameters: Albumin, total protein. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
Blood samples were collected from participants for analysis of following hematology parameters: Hemoglobin and MCHC. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Hematology Parameters: Hematocrit
Blood samples were collected from participants for analysis of following hematology parameters: Hematocrit. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count
Blood samples were collected from participants for analysis of following hematology parameters: Basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC, platelet count. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
Blood samples were collected from participants for analysis of following hematology parameter: Mean Corpuscle Hemoglobin. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
Blood samples were collected from participants for analysis of following hematology parameter: Mean Corpuscle Volume. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes
Blood samples were collected from participants for analysis of following hematology parameters: Red Blood Cell count, reticulocytes. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Number of Participants With Abnormal Values 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. Liver size was assessed as normal or abnormal. Data for abnormal (improved, worsened and unchanged) liver size is presented. End of study visit data is presented.
Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure
Physical examination included measurement of Jugular venous pressure. Jugular venous pressure was assessed as normal or abnormal. Data for abnormal (improved, worsened and unchanged) jugular venous pressure is presented. End of study visit data is presented.
Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites
Physical examination included measurement of ascites. Ascites were assessed as present or absent. Data for ascites present with improved, worsened and unchanged is presented. End of study visit data is presented.
Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema
Physical examination included measurement of peripheral edema. Peripheral edema were assessed as present or absent. Data for peripheral edema present with improved, worsened and unchanged is presented. End of study visit data is presented.
Percentage of Saturated Oxygen Level (Physical Examination Parameter)
Physical examination included measurement of saturated oxygen. End of study visit data is presented.
Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Vital Signs Parameter: Heart Rate
Heart rate was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Vital Signs Parameter: Weight
Weight was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Vital Sign Parameter: Height
Height was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Vital Sign Parameter: Body Mass Index
Body mass index was measured for the participants at indicated time points. Body mass index was calculated as weight in kilograms (kg) divided by the square of their height in meters (m^2). Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Vital Sign Parameter: Body Surface Area
Body surface area was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
12-lead ECG was measured in a semi-supine position using an automated ECG machine. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Data for any time till end of study were presented.
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at End of Study
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study
Estrone level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants
Estrone level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Female: Estriol at End of Study
Estriol level of female participants will be measured. Only those parameters having status as overall will be presented. Baseline is the last value recorded prior to start of study treatment from AMB112529. Change from Baseline is calculated by subtracting the Baseline value from the end of study post-dose visit value. Data for this endpoint will be available for this endpoint by June 2023
Change From Baseline in Plasma Endocrine Parameters - Female: Estriol at 20 Years of Age of Participants
Estriol level of female participants will be measured. Only those parameters having status as overall will be presented. Baseline is the last value recorded prior to start of study treatment from AMB112529.Change from Baseline is calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants. Data for this endpoint will be available for this endpoint by June 2023
Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study
Estradiol level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants
Estradiol level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at End of Study
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at 20 Years of Age of Participants
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at End of Study
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at 20 Years of Age of Participants
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study
Total Testosterone level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at 20 Years of Age of Participants
Total Testosterone level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study
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. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value. Data reported for left and right testicular volume.
Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants
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 as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants. Data reported for left and right testicular volume.
Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues
Time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, Phosphodiesterase type 5 [PDE-5] inhibitors) due to tolerability issues was defined as the time from randomization to the first occurrence of a dose change due to tolerability issues.
Secondary Outcome Measures
Number of Participants With All-cause Death
Number of participants with all-cause death is presented.
Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test
Participant's 6 MWD data has been presented into three categories as overall, with oxygen use and without oxygen use. The 6-minute walk test measures the distance that a participant can walk in 6 minutes. All participants were given standardized instructions and the distance walked was measured. Baseline which is the last value recorded prior to start of study treatment in AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time to the First Clinical Worsening of PAH
Time to clinical worsening of PAH is defined as the time from randomization to first occurrence of death (all cause), placed on active list for lung transplant, and/or atrial septostomy, hospitalization due to PAH deterioration, addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition, change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition, PAH related deterioration identified by increase in WHO functional class, deterioration in exercise testing (i.e., 20% decrease in 6MWD on two consecutive tests -1 week apart, clinical signs or symptoms of right sided heart failure (i.e., new peripheral edema, increase in liver size, ascites, increase in jugular venous pressure, pericardial effusion, increased dyspnea).
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition
Time to addition of another targeted PAH therapeutics agents due to deterioration of clinical condition was defined as the time from randomization to the first occurrence of deterioration of clinical condition.
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Lack of Beneficial Effect With Previous Therapy
The time to addition of another targeted PAH therapeutic agents due to lack of beneficial effect with previous therapy was defined as the time from randomization to the first occurrence of lack of beneficial effect with previous therapy (not reaching set treatment goals).
Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition
Time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition was defined as the time from randomization to the first occurrence of a dose change due to deterioration of clinical condition.
Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children
The short-form 10 (SF-10) Health Survey for children is a 10-item, 4-week recall, parent-completed health assessment that measures physical and psychosocial functioning for children ages five and over. 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. The aggregate score was then standardized and transformed to a norm-based scoring metric in accordance with the developer's guidelines. 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. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH
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 mapped to numeric scale for which scores ranged from 1-4 (i.e. Class I=1 and IV=4). Change categorization was based on change from Baseline scores: -2, -1, 0, +1, +2. Data was categorized as No Change (0), Improved (-1,-2), Deteriorated (+1,+2). Baseline was the last value recorded prior to start of study treatment from AMB112529. Higher score indicated higher severity.Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration
Blood samples were collected to analyze NT-Pro BNP concentration at specific time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01342952
Brief Title
Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
Official Title
An Open-label, Long Term Extension Study for Treatment of Pulmonary Arterial Hypertension in Paediatric Patients Aged 8 Years up to 18 Years Who Have Participated in AMB112529 and in Whom Continued Treatment With Ambrisentan is Desired
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
June 21, 2011 (Actual)
Primary Completion Date
June 9, 2022 (Actual)
Study Completion Date
June 9, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
An open label, long term extension to Study AMB112529. All subjects may remain in the extension study for a minimum of six months. Beyond the six month period, subjects may continue in the extension study until one of the following conditions is met:
the subject turns 18 years of age (when the subject can receive marketed product) the product is approved and available for use in the subject's age group, development for use in the paediatric population is discontinued. the subject decides he/she no longer wants to participate in the study, the investigator considers it is in the best interest of the subject to discontinue ambrisentan (e.g. for safety reasons).
The primary objective is the long-term safety and tolerability of ambrisentan in the paediatric PAH population. Secondary objectives are all cause mortality and change from baseline in Study AMB112529 on efficacy parameters.
Detailed Description
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 paediatric 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 long term paediatric study is to provide clinically relevant information on the long term safety of ambrisentan in children with the most common causes of PAH in this age group. This study is only open to patients who have participated in Study AMB112529, A randomized, open label study comparing safety and efficacy parameters for a high and a low dose of ambrisentan (adjusted for body weight) for the treatment of pulmonary arterial hypertension in paediatric patients aged 8 years up to 18 years, and in whom continued treatment with ambrisentan is warranted.
This study is part of a Paediatric Investigational Plan (PIP; EMEA-000434-PIP01-08) agreed with the European Medicines Agency's Paediatric Committee (PDCO).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary
Keywords
pulmonary arterial hypertension, pediatrics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ambrisentan
Arm Type
Experimental
Arm Description
Open label, flexible dosing from 2.5 mg to 10 mg (not to exceed 0.25 mg/kg) per day
Intervention Type
Drug
Intervention Name(s)
Ambrisentan
Intervention Description
open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day
Primary Outcome Measure Information:
Title
Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)
Description
AE was defined as any untoward medical occurrence in participant or clinical investigation participant,temporally associated with use of medicinal product, whether or not considered related to medicinal product.SAE was 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 congenital anomaly or birth defect, important medical events that may not immediately life threatening or result in death or hospitalization but may jeopardize participant or may require medical or surgical intervention as per medical or scientific judgement or associated with drug-induced liver injury.TEAE is any event that was not present prior to initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs which were not serious TEAEs were considered as non serious TEAEs.
Time Frame
Up to 10 years and 11 months
Title
Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin
Description
Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALT, AST, GGT, total bilirubin. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN)
Description
Blood samples were collected from participants for analysis of following clinical chemistry parameters: Calcium, chloride, CO2 content, glucose, potassium, magnesium, sodium, phosphorus inorganic, and BUN. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)
Description
Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALP, CK, LDH. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid
Description
Blood samples were collected from participants for analysis of following clinical chemistry parameters: Creatinine, uric acid. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Chemistry Parameters: Albumin, Total Protein
Description
Blood samples were collected from participants for analysis of following clinical chemistry parameters: Albumin, total protein. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
Description
Blood samples were collected from participants for analysis of following hematology parameters: Hemoglobin and MCHC. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Hematology Parameters: Hematocrit
Description
Blood samples were collected from participants for analysis of following hematology parameters: Hematocrit. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count
Description
Blood samples were collected from participants for analysis of following hematology parameters: Basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC, platelet count. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
Description
Blood samples were collected from participants for analysis of following hematology parameter: Mean Corpuscle Hemoglobin. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
Description
Blood samples were collected from participants for analysis of following hematology parameter: Mean Corpuscle Volume. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes
Description
Blood samples were collected from participants for analysis of following hematology parameters: Red Blood Cell count, reticulocytes. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size
Description
Physical examination included measurement of liver size. Any abnormal enlargement or reduction in the size of the liver is reported. Liver size was assessed as normal or abnormal. Data for abnormal (improved, worsened and unchanged) liver size is presented. End of study visit data is presented.
Time Frame
Up to 10 years and 11 months
Title
Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure
Description
Physical examination included measurement of Jugular venous pressure. Jugular venous pressure was assessed as normal or abnormal. Data for abnormal (improved, worsened and unchanged) jugular venous pressure is presented. End of study visit data is presented.
Time Frame
Up to 10 years and 11 months
Title
Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites
Description
Physical examination included measurement of ascites. Ascites were assessed as present or absent. Data for ascites present with improved, worsened and unchanged is presented. End of study visit data is presented.
Time Frame
Up to 10 years and 11 months
Title
Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema
Description
Physical examination included measurement of peripheral edema. Peripheral edema were assessed as present or absent. Data for peripheral edema present with improved, worsened and unchanged is presented. End of study visit data is presented.
Time Frame
Up to 10 years and 11 months
Title
Percentage of Saturated Oxygen Level (Physical Examination Parameter)
Description
Physical examination included measurement of saturated oxygen. End of study visit data is presented.
Time Frame
Up to 10 years and 11 months
Title
Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description
SBP and DBP was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Vital Signs Parameter: Heart Rate
Description
Heart rate was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Vital Signs Parameter: Weight
Description
Weight was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Vital Sign Parameter: Height
Description
Height was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Vital Sign Parameter: Body Mass Index
Description
Body mass index was measured for the participants at indicated time points. Body mass index was calculated as weight in kilograms (kg) divided by the square of their height in meters (m^2). Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Vital Sign Parameter: Body Surface Area
Description
Body surface area was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description
12-lead ECG was measured in a semi-supine position using an automated ECG machine. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Data for any time till end of study were presented.
Time Frame
Up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study
Description
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants
Description
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at End of Study
Description
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants
Description
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study
Description
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants
Description
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study
Description
Estrone level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants
Description
Estrone level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Estriol at End of Study
Description
Estriol level of female participants will be measured. Only those parameters having status as overall will be presented. Baseline is the last value recorded prior to start of study treatment from AMB112529. Change from Baseline is calculated by subtracting the Baseline value from the end of study post-dose visit value. Data for this endpoint will be available for this endpoint by June 2023
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Estriol at 20 Years of Age of Participants
Description
Estriol level of female participants will be measured. Only those parameters having status as overall will be presented. Baseline is the last value recorded prior to start of study treatment from AMB112529.Change from Baseline is calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants. Data for this endpoint will be available for this endpoint by June 2023
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study
Description
Estradiol level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants
Description
Estradiol level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study
Description
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants
Description
FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at End of Study
Description
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at 20 Years of Age of Participants
Description
Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at End of Study
Description
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at 20 Years of Age of Participants
Description
Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study
Description
Total Testosterone level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at 20 Years of Age of Participants
Description
Total Testosterone level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study
Description
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. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value. Data reported for left and right testicular volume.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants
Description
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 as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants. Data reported for left and right testicular volume.
Time Frame
Baseline (Day 1) and at 20 years of age of participants
Title
Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues
Description
Time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, Phosphodiesterase type 5 [PDE-5] inhibitors) due to tolerability issues was defined as the time from randomization to the first occurrence of a dose change due to tolerability issues.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Secondary Outcome Measure Information:
Title
Number of Participants With All-cause Death
Description
Number of participants with all-cause death is presented.
Time Frame
Up to 10 years and 11 months
Title
Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test
Description
Participant's 6 MWD data has been presented into three categories as overall, with oxygen use and without oxygen use. The 6-minute walk test measures the distance that a participant can walk in 6 minutes. All participants were given standardized instructions and the distance walked was measured. Baseline which is the last value recorded prior to start of study treatment in AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Time to the First Clinical Worsening of PAH
Description
Time to clinical worsening of PAH is defined as the time from randomization to first occurrence of death (all cause), placed on active list for lung transplant, and/or atrial septostomy, hospitalization due to PAH deterioration, addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition, change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition, PAH related deterioration identified by increase in WHO functional class, deterioration in exercise testing (i.e., 20% decrease in 6MWD on two consecutive tests -1 week apart, clinical signs or symptoms of right sided heart failure (i.e., new peripheral edema, increase in liver size, ascites, increase in jugular venous pressure, pericardial effusion, increased dyspnea).
Time Frame
Up to 10 years and 11 months
Title
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition
Description
Time to addition of another targeted PAH therapeutics agents due to deterioration of clinical condition was defined as the time from randomization to the first occurrence of deterioration of clinical condition.
Time Frame
Up to 10 years and 11 months
Title
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Lack of Beneficial Effect With Previous Therapy
Description
The time to addition of another targeted PAH therapeutic agents due to lack of beneficial effect with previous therapy was defined as the time from randomization to the first occurrence of lack of beneficial effect with previous therapy (not reaching set treatment goals).
Time Frame
Up to 10 years and 11 months
Title
Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition
Description
Time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition was defined as the time from randomization to the first occurrence of a dose change due to deterioration of clinical condition.
Time Frame
Up to 10 years and 11 months
Title
Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children
Description
The short-form 10 (SF-10) Health Survey for children is a 10-item, 4-week recall, parent-completed health assessment that measures physical and psychosocial functioning for children ages five and over. 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. The aggregate score was then standardized and transformed to a norm-based scoring metric in accordance with the developer's guidelines. 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. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH
Description
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 mapped to numeric scale for which scores ranged from 1-4 (i.e. Class I=1 and IV=4). Change categorization was based on change from Baseline scores: -2, -1, 0, +1, +2. Data was categorized as No Change (0), Improved (-1,-2), Deteriorated (+1,+2). Baseline was the last value recorded prior to start of study treatment from AMB112529. Higher score indicated higher severity.Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
Title
Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration
Description
Blood samples were collected to analyze NT-Pro BNP concentration at specific time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame
Baseline (Day 1) and up to 10 years and 11 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have participated in and complied, to the best of their ability, with the protocol for AMB112529 and have met one of the following:
Completed the Week 24 visit in AMB112529;
Required additional targeted treatment for PAH due to inadequate response to the current treatment or worsening of their clinical condition prior to week 24 in AMB112529;
Required reduction in dose of baseline targeted treatment for PAH after ambrisentan was added to the treatment regimen;
In the opinion of the investigator, continued treatment with ambrisentan is warranted.
A female is eligible to participate in this study, as assessed by the investigator, if she is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,
Child-bearing potential - has a negative pregnancy test and is not lactating and, if sexually active, agrees to continue to use 2 reliable methods of contraception until study completion and for at least 30 days following the last dose of study drug (reliable methods of contraception are listed in Appendix 2).
Subject or subject's legal guardian is able and willing to give written informed consent. As part of the consent, female subjects of childbearing potential will be informed of the risk of teratogenicity and will need to be counselled in a developmentally appropriate manner on the importance of pregnancy prevention; and male subjects will need to be informed of potential risk of testicular tubular atrophy and aspermia.
Exclusion Criteria:
Subjects who were withdrawn from ambrisentan in Study AMB112529;
Subjects who did not comply with the protocol in Study AMB112529;
Female subjects who are pregnant or breastfeeding;
Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min assessed within the previous 45 days) at the point of transition from Study AMB112529 into this study;
Subject with clinically significant fluid retention in the opinion of the investigator;
Subject with clinically significant anaemia in the opinion of the investigator;
Subjects who are to enter another clinical trial or be treated with another investigational product after exiting Study AMB112529.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
GSK Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-4204
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
GSK Investigational Site
City
Guymallen
State/Province
Mendoza
ZIP/Postal Code
5521
Country
Argentina
Facility Name
GSK Investigational Site
City
Ciudad de Buenos Aires
ZIP/Postal Code
1118
Country
Argentina
Facility Name
GSK Investigational Site
City
Córdoba
ZIP/Postal Code
5000
Country
Argentina
Facility Name
GSK Investigational Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
GSK Investigational Site
City
Pessac cedex
ZIP/Postal Code
33604
Country
France
Facility Name
GSK Investigational Site
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
GSK Investigational Site
City
Giessen
State/Province
Hessen
ZIP/Postal Code
35385
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
GSK Investigational Site
City
Budapest
ZIP/Postal Code
1096
Country
Hungary
Facility Name
GSK Investigational Site
City
Roma
State/Province
Lazio
ZIP/Postal Code
00165
Country
Italy
Facility Name
GSK Investigational Site
City
San Donato Milanese (MI)
State/Province
Lombardia
ZIP/Postal Code
20097
Country
Italy
Facility Name
GSK Investigational Site
City
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
104-8560
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
143-8541
Country
Japan
Facility Name
GSK Investigational Site
City
Kemerovo
ZIP/Postal Code
650002
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Moscow
ZIP/Postal Code
125412
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Novosibirsk
ZIP/Postal Code
630055
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
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