Hypertension, PulmonaryPhase 2NCT01342952
Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
A Phase 2 study testing Ambrisentan in people with Hypertension, Pulmonary, run by GlaxoSmithKline at 22 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 to 18 years
- Conditions the study is for
- Hypertension, Pulmonary
- What is being tested?
- Ambrisentan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 22 sitesin 9 countries
- Study dates
- 21 Jun 2011to 9 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
Trial locations and contacts
22 sites in 9 countries.
22 sites in 9 countries
United States4 sites
GSK Investigational Site
Ann Arbor, Michigan, 48109-4204
GSK Investigational Site
Aurora, Colorado, 80045
GSK Investigational Site
Boston, Massachusetts, 02115
GSK Investigational Site
New York, New York, 10032
Argentina3 sites
GSK Investigational Site
Ciudad de Buenos Aires, 1118
GSK Investigational Site
Córdoba, 5000
GSK Investigational Site
Guymallen, Mendoza Province, 5521
France3 sites
GSK Investigational Site
Paris, 75015
GSK Investigational Site
Pessac, 33604
GSK Investigational Site
Toulouse, 31059
Japan3 sites
GSK Investigational Site
Osaka, 565-0871
GSK Investigational Site
Tokyo, 104-8560
GSK Investigational Site
Tokyo, 143-8541
Russia3 sites
GSK Investigational Site
Kemerovo, 650002
GSK Investigational Site
Moscow, 125412
GSK Investigational Site
Novosibirsk, 630055
Germany2 sites
GSK Investigational Site
Berlin, 13353
GSK Investigational Site
Giessen, Hesse, 35385
Italy2 sites
GSK Investigational Site
Rome, Lazio, 00165
GSK Investigational Site
San Donato Milanese (MI), Lombardy, 20097
About this study
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
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.
Read the 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).
- Conditions
- Hypertension, Pulmonary
- Being tested
- Ambrisentan
- Keywords
- pulmonary arterial hypertension, pediatrics
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day
| Study group | Role | What they receive |
|---|---|---|
| Ambrisentan | Experimental | Open label, flexible dosing from 2.5 mg to 10 mg (not to exceed 0.25 mg/kg) per day Receives: Drug: Ambrisentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Up to 10 years and 11 months
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.
Measured: Up to 10 years and 11 months
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.
Measured: Up to 10 years and 11 months
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.
Measured: Up to 10 years and 11 months
Percentage of Saturated Oxygen Level (Physical Examination Parameter)
Physical examination included measurement of saturated oxygen. End of study visit data is presented.
Measured: Up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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
Measured: Baseline (Day 1) and up to 10 years and 11 months
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
Measured: Baseline (Day 1) and at 20 years of age of participants
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and 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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and at 20 years of age of participants
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
Secondary outcomes (9)
Number of Participants With All-cause Death
Number of participants with all-cause death is presented.
Measured: Up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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).
Measured: Up to 10 years and 11 months
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.
Measured: Up to 10 years and 11 months
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).
Measured: Up to 10 years and 11 months
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.
Measured: Up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
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.
Measured: Baseline (Day 1) and up to 10 years and 11 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2011 (estimated)
- Study start21 Jun 2011
- Primary completion9 Jun 2022
- Study completion9 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01342952
- Sponsor's protocol ID
- 114588
- Other IDs
- 2010-021572-29
- Status last verified
- Dec 2022
- First submitted
- 26 Apr 2011
- Last updated
- 30 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01342952
- Acronym / sponsor ID
- 114588
- Conditions
- Hypertension, Pulmonary
- Keywords
- pulmonary arterial hypertension, pediatrics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 21 Jun 2011 (actual)
- Primary completion
- 9 Jun 2022 (actual)
- Study completion
- 9 Jun 2022 (actual)
- First posted
- 27 Apr 2011 (estimated)
- Results
- Posted 30 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ambrisentan | Experimental | Drug: AmbrisentanOpen label, flexible dosing from 2.5 mg to 10 mg (not to exceed 0.25 mg/kg) per day |
Who may qualify
- Ages
- 8 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Have participated in and complied, to the best of their ability, with the protocol for AMB112529 and have met one of the following:
- A female is eligible to participate in this study, as assessed by the investigator, if she is of:
- 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.
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ambrisentanopen label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day | Drug | Ambrisentan |
Primary outcome
Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)
Time frame: Up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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)
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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)
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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)
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Up to 10 years and 11 months
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
Time frame: Up to 10 years and 11 months
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
Time frame: Up to 10 years and 11 months
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
Time frame: Up to 10 years and 11 months
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)
Time frame: Up to 10 years and 11 months
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)
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
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
Time frame: Baseline (Day 1) and 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 frame: Baseline (Day 1) and up to 10 years and 11 months
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.
9 secondary outcomes
Number of Participants With All-cause Death
Time frame: Up to 10 years and 11 months
Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Time to the First Clinical Worsening of PAH
Time frame: Up to 10 years and 11 months
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition
Time frame: Up to 10 years and 11 months
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Lack of Beneficial Effect With Previous Therapy
Time frame: Up to 10 years and 11 months
Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition
Time frame: Up to 10 years and 11 months
Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
22 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ambrisentan in people with Hypertension, Pulmonary, run by GlaxoSmithKline at 22 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Argentina, France, Japan, Russia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) (time frame: Up to 10 years and 11 months). The study lists 47 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2022.