Hypertension, Pulmonary
Conditions
Keywords
pulmonary arterial hypertension, pediatrics
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).
Interventions
DRUGAmbrisentan
open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
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: 1. Completed the Week 24 visit in AMB112529; 2. 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; 3. Required reduction in dose of baseline targeted treatment for PAH after ambrisentan was added to the treatment regimen; 4. 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: 1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or, 2. 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.
Design outcomes
Primary
| Measure | Time frame | 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 | 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. |
| Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | 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 | 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) | 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) | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Baseline (Day 1) and up to 10 years and 11 months | 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 | Up to 10 years and 11 months | 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 | Up to 10 years and 11 months | 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 | Up to 10 years and 11 months | 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 | 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 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 | Baseline (Day 1) and up to 10 years and 11 months | 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 | Baseline (Day 1) and up to 10 years and 11 months | 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 | Baseline (Day 1) and up to 10 years and 11 months | 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. |
| Number of Participants With All-cause Death | Up to 10 years and 11 months | Number of participants with all-cause death is presented. |
Countries
Argentina, France, Germany, Hungary, Italy, Japan, Russia, Spain, United States
Participant flow
Recruitment details
This was an open label, long term extension of study AMB112529 (NCT01342952) which evaluated safety and tolerability of ambrisentan in the pediatric (aged 8 years up to 18 years) Pulmonary Arterial Hypertension (PAH) population.
Pre-assignment details
A total of 38 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Ambrisentan 2.5 mg (ITT) Participants received ambrisentan 2.5 milligrams (mg) dose of ambrisentan orally in tablet/s form once daily. The Intent-to-Treat (ITT) Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588. | 9 |
| Ambrisentan 5 mg (ITT) Participants received 5 mg dose of ambrisenten orally in tablet form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588. | 19 |
| Ambrisentan 7.5 mg (ITT) Participants received 7.5 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588. | 5 |
| Ambrisentan 10 mg (ITT) Participants received 10 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588. | 5 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Overall Study | Physician Decision | 3 | 3 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Ambrisentan 2.5 mg (ITT) | Ambrisentan 5 mg (ITT) | Ambrisentan 7.5 mg (ITT) | Ambrisentan 10 mg (ITT) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 9.7 Years STANDARD_DEVIATION 2.29 | 11.9 Years STANDARD_DEVIATION 2.57 | 12.6 Years STANDARD_DEVIATION 2.61 | 15.2 Years STANDARD_DEVIATION 0.84 | 11.9 Years STANDARD_DEVIATION 2.81 |
| Race/Ethnicity, Customized African American/African Heritage | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 4 Participants | 14 Participants | 4 Participants | 5 Participants | 27 Participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 4 Participants | 5 Participants | 25 Participants |
| Sex: Female, Male Male | 2 Participants | 10 Participants | 1 Participants | 0 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 4 / 16 | 1 / 6 | 2 / 12 |
| other Total, other adverse events | 3 / 4 | 13 / 16 | 5 / 6 | 10 / 12 |
| serious Total, serious adverse events | 2 / 4 | 7 / 16 | 4 / 6 | 8 / 12 |
Outcome results
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Albumin | -3.3 Grams per liter | Standard Deviation 4.04 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Total protein | -3.7 Grams per liter | Standard Deviation 4.51 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Total protein | -3.4 Grams per liter | Standard Deviation 4.93 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Albumin | -1.2 Grams per liter | Standard Deviation 3.16 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Albumin | 1.6 Grams per liter | Standard Deviation 1.14 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Total protein | 3.0 Grams per liter | Standard Deviation 5.24 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Albumin | -2.0 Grams per liter | Standard Deviation 4.42 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Albumin, Total Protein | Total protein | -3.0 Grams per liter | Standard Deviation 7.33 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | ALP | -77.7 International units per Liter | Standard Deviation 57.01 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | LDH | -40.3 International units per Liter | Standard Deviation 45.54 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | CK | -18.7 International units per Liter | Standard Deviation 23.07 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | ALP | -109.5 International units per Liter | Standard Deviation 71.51 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | LDH | -48.9 International units per Liter | Standard Deviation 71.64 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | CK | 4.0 International units per Liter | Standard Deviation 100.83 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | ALP | -148.8 International units per Liter | Standard Deviation 151.78 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | CK | 46.6 International units per Liter | Standard Deviation 89.55 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | LDH | -12.8 International units per Liter | Standard Deviation 22.58 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | ALP | -135.6 International units per Liter | Standard Deviation 97.33 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | LDH | -28.3 International units per Liter | Standard Deviation 37.23 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) | CK | -9.7 International units per Liter | Standard Deviation 13.96 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Glucose | 0.167 Millimoles per liter | Standard Deviation 0.4163 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Chloride | 1.7 Millimoles per liter | Standard Deviation 5.13 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Phosphorus inorganic | -0.340 Millimoles per liter | Standard Deviation 0.1311 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | CO2 content | -0.3 Millimoles per liter | Standard Deviation 2.89 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Sodium | 2.7 Millimoles per liter | Standard Deviation 1.15 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Magnesium | -0.100 Millimoles per liter | Standard Deviation 0.0872 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Calcium | -0.150 Millimoles per liter | Standard Deviation 0.1769 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | BUN | -0.10 Millimoles per liter | Standard Deviation 1.808 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Potassium | -0.30 Millimoles per liter | Standard Deviation 0.529 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Glucose | -0.150 Millimoles per liter | Standard Deviation 1.1414 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | BUN | -0.51 Millimoles per liter | Standard Deviation 1.649 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Calcium | -0.054 Millimoles per liter | Standard Deviation 0.0779 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Chloride | 2.6 Millimoles per liter | Standard Deviation 1.65 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | CO2 content | 2.2 Millimoles per liter | Standard Deviation 1.87 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Potassium | -0.07 Millimoles per liter | Standard Deviation 0.337 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Magnesium | -0.062 Millimoles per liter | Standard Deviation 0.0898 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Sodium | 1.0 Millimoles per liter | Standard Deviation 1.63 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Phosphorus inorganic | -0.159 Millimoles per liter | Standard Deviation 0.3055 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Magnesium | 0.028 Millimoles per liter | Standard Deviation 0.0683 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Calcium | 0.028 Millimoles per liter | Standard Deviation 0.063 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | BUN | -0.14 Millimoles per liter | Standard Deviation 1.274 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Phosphorus inorganic | -0.212 Millimoles per liter | Standard Deviation 0.344 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Glucose | 0.120 Millimoles per liter | Standard Deviation 0.5541 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Chloride | 0.4 Millimoles per liter | Standard Deviation 3.44 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Sodium | -0.2 Millimoles per liter | Standard Deviation 0.84 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | CO2 content | 0.2 Millimoles per liter | Standard Deviation 3.7 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Potassium | -0.02 Millimoles per liter | Standard Deviation 0.148 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | CO2 content | 0.0 Millimoles per liter | Standard Deviation 1.8 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Glucose | 0.478 Millimoles per liter | Standard Deviation 0.9107 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Sodium | 0.7 Millimoles per liter | Standard Deviation 1.87 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Potassium | -0.12 Millimoles per liter | Standard Deviation 0.327 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | BUN | 0.33 Millimoles per liter | Standard Deviation 1.507 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Phosphorus inorganic | -0.108 Millimoles per liter | Standard Deviation 0.2408 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Magnesium | 0.012 Millimoles per liter | Standard Deviation 0.0716 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Chloride | -0.6 Millimoles per liter | Standard Deviation 2.96 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) | Calcium | -0.060 Millimoles per liter | Standard Deviation 0.1075 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Uric acid | -64.67 Micromoles per liter | Standard Deviation 119.169 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Creatinine | 6.27 Micromoles per liter | Standard Deviation 19.775 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Uric acid | -83.60 Micromoles per liter | Standard Deviation 90.103 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Creatinine | 8.16 Micromoles per liter | Standard Deviation 9.602 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Creatinine | 10.26 Micromoles per liter | Standard Deviation 8.008 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Uric acid | -45.40 Micromoles per liter | Standard Deviation 77.584 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Creatinine | 19.31 Micromoles per liter | Standard Deviation 14.698 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid | Uric acid | 21.22 Micromoles per liter | Standard Deviation 79.33 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -1.70 Picograms | Standard Deviation 3.315 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -1.46 Picograms | Standard Deviation 2.823 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -0.70 Picograms | Standard Deviation 1.512 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | 0.11 Picograms | Standard Deviation 1.981 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | -2.3 Femtoliters | Standard Deviation 6.66 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | -1.0 Femtoliters | Standard Deviation 5.52 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | -0.8 Femtoliters | Standard Deviation 2.68 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | 0.8 Femtoliters | Standard Deviation 5.61 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Basophils | -0.007 Giga cells per Liter | Standard Deviation 0.0153 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | WBC | -0.67 Giga cells per Liter | Standard Deviation 2.616 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Total neutrophils | 0.677 Giga cells per Liter | Standard Deviation 1.9014 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Eosinophils | -0.210 Giga cells per Liter | Standard Deviation 0.4139 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Platelet count | -34.0 Giga cells per Liter | Standard Deviation 27.18 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Lymphocytes | -1.107 Giga cells per Liter | Standard Deviation 0.731 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Monocytes | -0.013 Giga cells per Liter | Standard Deviation 0.155 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | WBC | -1.22 Giga cells per Liter | Standard Deviation 2.072 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Monocytes | 0.040 Giga cells per Liter | Standard Deviation 0.1273 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Lymphocytes | -0.329 Giga cells per Liter | Standard Deviation 1.1373 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Total neutrophils | -0.974 Giga cells per Liter | Standard Deviation 1.2239 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Platelet count | -29.3 Giga cells per Liter | Standard Deviation 50.03 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Eosinophils | 0.034 Giga cells per Liter | Standard Deviation 0.1096 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Basophils | 0.019 Giga cells per Liter | Standard Deviation 0.0417 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Monocytes | -0.006 Giga cells per Liter | Standard Deviation 0.1635 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Basophils | -0.006 Giga cells per Liter | Standard Deviation 0.0152 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Eosinophils | -0.026 Giga cells per Liter | Standard Deviation 0.0602 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Lymphocytes | -0.152 Giga cells per Liter | Standard Deviation 0.6937 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Total neutrophils | 0.412 Giga cells per Liter | Standard Deviation 0.6278 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | WBC | 0.22 Giga cells per Liter | Standard Deviation 0.421 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Platelet count | -9.2 Giga cells per Liter | Standard Deviation 30.87 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Lymphocytes | -0.394 Giga cells per Liter | Standard Deviation 1.1063 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Platelet count | -0.4 Giga cells per Liter | Standard Deviation 64.78 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | WBC | 0.18 Giga cells per Liter | Standard Deviation 2.787 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Eosinophils | 0.009 Giga cells per Liter | Standard Deviation 0.0746 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Basophils | -0.002 Giga cells per Liter | Standard Deviation 0.0148 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Total neutrophils | 0.524 Giga cells per Liter | Standard Deviation 2.003 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count | Monocytes | 0.037 Giga cells per Liter | Standard Deviation 0.1986 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Hematocrit | -0.0610 Proportion of red blood cells in blood | Standard Deviation 0.10235 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Hematocrit | -0.0004 Proportion of red blood cells in blood | Standard Deviation 0.04543 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Hematocrit | 0.0100 Proportion of red blood cells in blood | Standard Deviation 0.02884 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Hematocrit | 0.0040 Proportion of red blood cells in blood | Standard Deviation 0.06572 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | Hemoglobin | -23.0 Grams per Liter | Standard Deviation 38.63 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | MCHC | -9.3 Grams per Liter | Standard Deviation 16.01 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | MCHC | -12.4 Grams per Liter | Standard Deviation 17.31 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | Hemoglobin | -4.7 Grams per Liter | Standard Deviation 16.15 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | MCHC | -6.0 Grams per Liter | Standard Deviation 12.98 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | Hemoglobin | 0.8 Grams per Liter | Standard Deviation 9.71 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | Hemoglobin | 1.3 Grams per Liter | Standard Deviation 20.12 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) | MCHC | -1.1 Grams per Liter | Standard Deviation 11.72 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Red Blood Cell count | -0.57 Trillion cells per liter | Standard Deviation 0.862 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Reticulocytes | 0.01427 Trillion cells per liter | Standard Deviation 0.024625 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Reticulocytes | -0.00816 Trillion cells per liter | Standard Deviation 0.043615 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Red Blood Cell count | 0.07 Trillion cells per liter | Standard Deviation 0.387 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Red Blood Cell count | 0.14 Trillion cells per liter | Standard Deviation 0.251 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Reticulocytes | 0.00906 Trillion cells per liter | Standard Deviation 0.013265 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Red Blood Cell count | 0.00 Trillion cells per liter | Standard Deviation 0.497 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes | Reticulocytes | 0.01843 Trillion cells per liter | Standard Deviation 0.041832 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | ALT | -7.5 Millimoles per liter | Standard Deviation 12.56 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | GGT | -0.5 Millimoles per liter | Standard Deviation 15 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | Total bilirubin | -5.3 Millimoles per liter | Standard Deviation 12.47 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | AST | -11.8 Millimoles per liter | Standard Deviation 6.29 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | ALT | -1.0 Millimoles per liter | Standard Deviation 8.64 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | AST | -5.6 Millimoles per liter | Standard Deviation 7.23 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | GGT | -7.0 Millimoles per liter | Standard Deviation 10.45 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | Total bilirubin | -4.0 Millimoles per liter | Standard Deviation 3.3 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | GGT | -0.8 Millimoles per liter | Standard Deviation 8.44 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | Total bilirubin | -2.8 Millimoles per liter | Standard Deviation 6.06 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | ALT | 0.8 Millimoles per liter | Standard Deviation 4.09 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | AST | -1.0 Millimoles per liter | Standard Deviation 2.55 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | Total bilirubin | 3.1 Millimoles per liter | Standard Deviation 8.45 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | ALT | 4.0 Millimoles per liter | Standard Deviation 7.42 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | GGT | -4.6 Millimoles per liter | Standard Deviation 28.3 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin | AST | -2.1 Millimoles per liter | Standard Deviation 8.13 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants | 55.50 Picomoles per liter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants | -107.00 Picomoles per liter | — |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants | 15.00 Picomoles per liter | — |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants | 387.50 Picomoles per liter | Standard Deviation 375.474 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study | -11.00 Picomoles per liter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study | -77.25 Picomoles per liter | Standard Deviation 211.435 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study | -255.50 Picomoles per liter | Standard Deviation 427.8 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study | 44.80 Picomoles per liter | Standard Deviation 264.452 |
Primary
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
Time frame: Baseline (Day 1) and at 20 years of age of participants
Primary
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
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants | -7.00 Picomole per milliliter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants | 179.00 Picomole per milliliter | Standard Deviation 196.576 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants | 11.00 Picomole per milliliter | — |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants | 89.00 Picomole per milliliter | Standard Deviation 73.539 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study | 0.00 Picomole per milliliter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study | -6.80 Picomole per milliliter | Standard Deviation 178.361 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study | -26.00 Picomole per milliliter | Standard Deviation 209.304 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study | 17.00 Picomole per milliliter | Standard Deviation 125.913 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | FSH | 35.800 International units per Liter | — |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | LH | 8.60 International units per Liter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | LH | 6.17 International units per Liter | Standard Deviation 16.717 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | FSH | 0.800 International units per Liter | Standard Deviation 1.253 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | FSH | -2.500 International units per Liter | — |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | LH | -6.30 International units per Liter | — |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | FSH | 0.967 International units per Liter | Standard Deviation 0.3055 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants | LH | 5.10 International units per Liter | Standard Deviation 4.597 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | FSH | 0.200 International units per Liter | Standard Deviation 1.249 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | LH | 0.03 International units per Liter | Standard Deviation 0.058 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | LH | 5.17 International units per Liter | Standard Deviation 9.665 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | FSH | 3.217 International units per Liter | Standard Deviation 4.0455 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | FSH | 0.100 International units per Liter | Standard Deviation 3.6042 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | LH | 4.17 International units per Liter | Standard Deviation 9.563 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | FSH | -0.336 International units per Liter | Standard Deviation 3.7053 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study | LH | 0.61 International units per Liter | Standard Deviation 9.778 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants | 0.0 Nanogram per liter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants | 49.0 Nanogram per liter | Standard Deviation 110.31 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants | 37.0 Nanogram per liter | — |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants | 7.5 Nanogram per liter | Standard Deviation 70 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. At end of study, participants did not receive Ambrisentan 7.5 mg dose for evaluation of Inhibin B hence N=0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at End of Study | 0.0 Nanogram per liter | Standard Deviation 11.31 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at End of Study | 14.0 Nanogram per liter | Standard Deviation 67.48 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at End of Study | -29.0 Nanogram per liter | Standard Deviation 27.6 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants | 49.0 Nanomoles per liter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants | 1.7 Nanomoles per liter | Standard Deviation 54.37 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants | 10.0 Nanomoles per liter | — |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants | -15.5 Nanomoles per liter | Standard Deviation 2.12 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study | -10.0 Nanomoles per liter | Standard Deviation 1.41 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study | 11.8 Nanomoles per liter | Standard Deviation 14.22 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study | 0.5 Nanomoles per liter | Standard Deviation 0.71 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study | 17.3 Nanomoles per liter | Standard Deviation 22.31 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants | FSH | 2.350 International unit per Liter | Standard Deviation 3.6062 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants | LH | 2.90 International unit per Liter | Standard Deviation 2.828 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants | FSH | 0.500 International unit per Liter | — |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants | LH | 0.60 International unit per Liter | — |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | FSH | 6.000 International units per Liter | — |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | LH | 3.20 International units per Liter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | LH | 1.70 International units per Liter | Standard Deviation 1.473 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | FSH | 0.267 International units per Liter | Standard Deviation 0.3215 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | LH | 3.55 International units per Liter | Standard Deviation 2.333 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | FSH | 3.250 International units per Liter | Standard Deviation 3.4648 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | LH | 3.55 International units per Liter | Standard Deviation 4.738 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study | FSH | 0.850 International units per Liter | Standard Deviation 2.4749 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at 20 Years of Age of Participants | 23.0 Nanogram per liter | Standard Deviation 21.21 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at 20 Years of Age of Participants | -47.0 Nanogram per liter | — |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No participants were analyzed for evaluation of Inhibin B in Ambrisentan 2.5 mg arm, hence N=0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at End of Study | 15.0 Nanogram per liter | Standard Deviation 5.66 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at End of Study | 8.5 Nanogram per liter | Standard Deviation 6.36 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at End of Study | 73.0 Nanogram per liter | Standard Deviation 175.36 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at 20 Years of Age of Participants | -2.5 Nanomoles per liter | Standard Deviation 12.02 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at 20 Years of Age of Participants | 12.0 Nanomoles per liter | — |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. At end of study, no participants were analyzed for evaluation of Sex harmone binding globulin in 2.5 mg dose, hence N=0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at End of Study | -28.5 Nanomoles per liter | Standard Deviation 28.99 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at End of Study | -11.5 Nanomoles per liter | Standard Deviation 3.54 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at End of Study | -11.0 Nanomoles per liter | Standard Deviation 39.6 |
Primary
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.
Time frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at 20 Years of Age of Participants | 4.000 Nanomoles per liter | Standard Deviation 10.748 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at 20 Years of Age of Participants | 6.600 Nanomoles per liter | — |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study | 10.650 Nanomoles per liter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study | 2.900 Nanomoles per liter | Standard Deviation 7.119 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study | 7.300 Nanomoles per liter | Standard Deviation 1.6971 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study | 17.175 Nanomoles per liter | Standard Deviation 0.1061 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Mass Index | 2.65 Kilogram per meter square | Standard Deviation 2.195 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Mass Index | 2.45 Kilogram per meter square | Standard Deviation 1.828 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Mass Index | 1.52 Kilogram per meter square | Standard Deviation 1.633 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Mass Index | 1.99 Kilogram per meter square | Standard Deviation 2.642 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Surface Area | 0.398 Meter square | Standard Deviation 0.3024 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Surface Area | 0.207 Meter square | Standard Deviation 0.1744 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Surface Area | 0.144 Meter square | Standard Deviation 0.1254 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Vital Sign Parameter: Body Surface Area | 0.236 Meter square | Standard Deviation 0.3163 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Height | 25.3 Centimeters | Standard Deviation 19.99 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Height | 9.9 Centimeters | Standard Deviation 9.92 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Vital Sign Parameter: Height | 7.2 Centimeters | Standard Deviation 9.47 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Vital Sign Parameter: Height | 12.1 Centimeters | Standard Deviation 17.55 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Heart Rate | -9.0 Beats per minute | Standard Deviation 13.44 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Heart Rate | -4.0 Beats per minute | Standard Deviation 8.08 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Heart Rate | -3.8 Beats per minute | Standard Deviation 11.5 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Vital Signs Parameter: Heart Rate | -6.0 Beats per minute | Standard Deviation 15.06 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 16.3 Millimeters of mercury | Standard Deviation 16.38 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 1.5 Millimeters of mercury | Standard Deviation 5.8 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 2.3 Millimeters of mercury | Standard Deviation 12.7 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 8.4 Millimeters of mercury | Standard Deviation 17.99 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 1.2 Millimeters of mercury | Standard Deviation 18.63 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 3.6 Millimeters of mercury | Standard Deviation 16.96 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 8.5 Millimeters of mercury | Standard Deviation 12.22 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 2.1 Millimeters of mercury | Standard Deviation 9.67 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Weight | 17.43 Kilograms | Standard Deviation 12.695 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Weight | 10.73 Kilograms | Standard Deviation 8.628 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Vital Signs Parameter: Weight | 7.12 Kilograms | Standard Deviation 5.346 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Vital Signs Parameter: Weight | 12.17 Kilograms | Standard Deviation 16.3 |
Primary
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 frame: Baseline (Day 1) and at 20 years of age of participants
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No participants were analyzed for evaluation of testicular volume in 2.5 mg dose, hence N=0
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 5 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants | Left TV | 17.0 Milliliter | — |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants | Right TV | 15.0 Milliliter | Standard Deviation 7.07 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants | Left TV | 16.5 Milliliter | Standard Deviation 4.95 |
| Ambrisentan 10 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants | Right TV | 8.0 Milliliter | — |
| Ambrisentan 10 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants | Left TV | 8.0 Milliliter | — |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No participants were analyzed for evaluation of testicular volume in 2.5 mg dose, hence N=0
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 5 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study | Right TV | 0.0 Milliliter | — |
| Ambrisentan 5 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study | Left TV | 6.0 Milliliter | Standard Deviation 8.49 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study | Right TV | 15.0 Milliliter | Standard Deviation 7.07 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study | Left TV | 16.5 Milliliter | Standard Deviation 4.95 |
| Ambrisentan 10 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study | Right TV | 11.5 Milliliter | Standard Deviation 16.26 |
| Ambrisentan 10 mg (Safety) | Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study | Left TV | 13.0 Milliliter | Standard Deviation 14.14 |
Primary
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.
Time frame: Up to 10 years and 11 months
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, not clinically significant | 4 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, clinically significant | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, clinically significant | 2 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, not clinically significant | 14 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, not clinically significant | 3 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, clinically significant | 1 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, not clinically significant | 9 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal, clinically significant | 3 Participants |
Primary
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.
Time frame: Up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Improved | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Unchanged | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Worsened | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Improved | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Unchanged | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Improved | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Unchanged | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Improved | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Unchanged | 2 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure | Jugular Venous Pressure: Abnormal: Worsened | 0 Participants |
Primary
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.
Time frame: Up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Improved | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Unchanged | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Worsened | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Improved | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Unchanged | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Improved | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Unchanged | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Improved | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Unchanged | 2 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size | Liver Size: Abnormal: Worsened | 0 Participants |
Primary
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.
Time frame: Up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Improved | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Unchanged | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Worsened | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Improved | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Unchanged | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Improved | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Unchanged | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Improved | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Unchanged | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema | Peripheral edema: Present: Worsened | 0 Participants |
Primary
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.
Time frame: Up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Improved | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Unchanged | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Worsened | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Improved | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Unchanged | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Worsened | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Improved | 0 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Unchanged | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Improved | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Unchanged | 2 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites | Ascites: Present: Worsened | 0 Participants |
Primary
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.
Time frame: Up to 10 years and 11 months
Population: Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | Non-STEAEs | 3 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | STEAEs | 2 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | STEAEs | 7 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | Non-STEAEs | 13 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | Non-STEAEs | 5 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | STEAEs | 4 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | Non-STEAEs | 10 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) | STEAEs | 8 Participants |
Primary
Percentage of Saturated Oxygen Level (Physical Examination Parameter)
Physical examination included measurement of saturated oxygen. End of study visit data is presented.
Time frame: Up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Percentage of Saturated Oxygen Level (Physical Examination Parameter) | 95.5 Percentage of oxygen saturation | Standard Deviation 4.2 |
| Ambrisentan 5 mg (Safety) | Percentage of Saturated Oxygen Level (Physical Examination Parameter) | 96.8 Percentage of oxygen saturation | Standard Deviation 2.04 |
| Ambrisentan 7.5 mg (Safety) | Percentage of Saturated Oxygen Level (Physical Examination Parameter) | 97.4 Percentage of oxygen saturation | Standard Deviation 1.34 |
| Ambrisentan 10 mg (Safety) | Percentage of Saturated Oxygen Level (Physical Examination Parameter) | 96.9 Percentage of oxygen saturation | Standard Deviation 1.97 |
Primary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: Safety Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues | 393.0 Days | — |
| Ambrisentan 5 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues | 468.5 Days | Standard Deviation 41.72 |
| Ambrisentan 7.5 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues | 354.0 Days | — |
| Ambrisentan 10 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues | 1448.7 Days | Standard Deviation 745.09 |
Secondary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: ITT Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Physical health summary | -1.618 Scores on a scale | Standard Deviation 7.465 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Psychosocial summary | -0.336 Scores on a scale | Standard Deviation 5.429 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Psychosocial summary | -1.880 Scores on a scale | Standard Deviation 7.981 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Physical health summary | -0.967 Scores on a scale | Standard Deviation 16.489 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Physical health summary | -1.788 Scores on a scale | Standard Deviation 12.0104 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Psychosocial summary | 2.225 Scores on a scale | Standard Deviation 6.2357 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Physical health summary | -0.272 Scores on a scale | Standard Deviation 15.1029 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children | Psychosocial summary | 6.766 Scores on a scale | Standard Deviation 6.508 |
Secondary
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 frame: Baseline (Day 1) and up to 10 years and 11 months
Population: ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to their treatment group at the start of study AMB114588. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Without oxygen use | 130.41 Meters | Standard Deviation 104.115 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Overall | 98.53 Meters | Standard Deviation 115.355 |
| Ambrisentan 2.5 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | With oxygen use | -13.05 Meters | Standard Deviation 96.944 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Without oxygen use | 56.74 Meters | Standard Deviation 58.069 |
| Ambrisentan 5 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Overall | 56.74 Meters | Standard Deviation 58.069 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Without oxygen use | 3.05 Meters | Standard Deviation 94.659 |
| Ambrisentan 7.5 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Overall | 3.05 Meters | Standard Deviation 94.659 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Overall | 34.24 Meters | Standard Deviation 72.135 |
| Ambrisentan 10 mg (Safety) | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Without oxygen use | 34.24 Meters | Standard Deviation 72.135 |
Secondary
Number of Participants With All-cause Death
Number of participants with all-cause death is presented.
Time frame: Up to 10 years and 11 months
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With All-cause Death | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With All-cause Death | 4 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With All-cause Death | 1 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With All-cause Death | 2 Participants |
Secondary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: ITT Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Improved | 5 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Deteriorated | 0 Participants |
| Ambrisentan 2.5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | No Change | 4 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Improved | 5 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Deteriorated | 0 Participants |
| Ambrisentan 5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | No Change | 6 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | No Change | 1 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Improved | 3 Participants |
| Ambrisentan 7.5 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Deteriorated | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Improved | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | Deteriorated | 0 Participants |
| Ambrisentan 10 mg (Safety) | Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH | No Change | 5 Participants |
Secondary
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.
Time frame: Baseline (Day 1) and up to 10 years and 11 months
Population: ITT Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration | -62.59 Percentage Change |
| Ambrisentan 5 mg (Safety) | Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration | -56.02 Percentage Change |
| Ambrisentan 7.5 mg (Safety) | Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration | 59.06 Percentage Change |
| Ambrisentan 10 mg (Safety) | Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration | 101.96 Percentage Change |
Secondary
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.
Time frame: Up to 10 years and 11 months
Population: ITT Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition | 1247.3 Days | Standard Deviation 1051.97 |
| Ambrisentan 5 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition | 1097.0 Days | Standard Deviation 922.77 |
| Ambrisentan 7.5 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition | 909.0 Days | — |
| Ambrisentan 10 mg (Safety) | Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition | 345.5 Days | Standard Deviation 109.6 |
Secondary
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 frame: Up to 10 years and 11 months
Population: ITT Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition | 510.0 Days | — |
| Ambrisentan 5 mg (Safety) | Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition | 697.5 Days | Standard Deviation 863.38 |
| Ambrisentan 7.5 mg (Safety) | Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition | 909.0 Days | — |
| Ambrisentan 10 mg (Safety) | Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition | 345.5 Days | Standard Deviation 109.6 |
Secondary
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 frame: Up to 10 years and 11 months
Population: ITT Population. Only those participants with available data at the specified time points were analyzed. Participants in higher dose group (7.5 and 10 mg) were not taking any additional therapeutic PAH agent hence N=0.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Lack of Beneficial Effect With Previous Therapy | 315.5 Days | Standard Deviation 2.12 |
| Ambrisentan 5 mg (Safety) | Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Lack of Beneficial Effect With Previous Therapy | 173.0 Days | — |
Secondary
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 frame: Up to 10 years and 11 months
Population: ITT Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan 2.5 mg (Safety) | Time to the First Clinical Worsening of PAH | 315.5 Days | Standard Deviation 2.12 |
| Ambrisentan 5 mg (Safety) | Time to the First Clinical Worsening of PAH | 896.2 Days | Standard Deviation 721.33 |
| Ambrisentan 7.5 mg (Safety) | Time to the First Clinical Worsening of PAH | 1122.0 Days | Standard Deviation 704.09 |
| Ambrisentan 10 mg (Safety) | Time to the First Clinical Worsening of PAH | 228.0 Days | — |