Pulmonary Hypertension
Conditions
Brief summary
This Phase 2 study was to determine the incidence of increased serum aminotransferase concentrations (alanine aminotransferase \[ALT\] and/or aspartate aminotransferase \[AST\]), as well as the overall safety and tolerability of ambrisentan, in participants with pulmonary arterial hypertension (PAH), idiopathic PAH (IPAH), or familial PAH (FPAH) who had previously discontinued ERA therapy (bosentan or sitaxsentan) due to increased serum ALT or AST concentrations.
Interventions
DRUGambrisentan
All eligible subjects received 2.5 mg ambrisentan once daily for a period of 4 weeks before increasing the dose to 5 mg once daily. After Week 24, investigators were allowed to adjust the dose of ambrisentan as clinically indicated (available doses were 2.5, 5, and 10 mg).
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Summary of Inclusion Criteria: * Males and Females between 12 and 75 years of age * Current diagnosis of IPAH, FPAH, or PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts, anorexigen use, HIV infection * Must have previously discontinued bosentan or sitaxsentan therapy due to serum aminotransferase (ALT and/or AST) concentrations \> 3 x ULN * Must have normal (\< 1 x ULN) serum ALT and AST concentrations at screening * Six-minute Walk distance of at least 150 meters at screening * If receiving sildenafil or a clinically approved prostanoid for PAH, must have been on stable therapy for at least 4 weeks prior to screening * Subjects with a diagnosis of HIV must have stable disease status during the screening period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Confirmed Serum Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Concentrations > 3 x the Upper Limit of Normal (ULN) Considered to be Related to Ambrisentan and Resulted in Discontinuation of Study Drug. | Week 12 | The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations \> 3 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in discontinuation of study drug. Safety analysis set included all participants who received at least 1 dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Confirmed Serum ALT or AST Concentrations > 3 x ULN That Were Related to Ambrisentan and Resulted in Dose Reduction | Week 12 | The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations \> 3 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in dose reduction. Safety analysis set included all participants who received at least 1 dose of study drug. |
| A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in the 6-Minute Walk Distance Test (6MWD) | Baseline to Week 12 | The 6MWD test is a measure of exercise tolerance, and measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. |
| A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Borg Dyspnea Index Immediately Following Exercise | Baseline to Week 12 | Change from baseline evaluated after 12 weeks of ambrisentan therapy in Borg dyspnea index (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness). |
| A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class | Baseline to Week 12 | Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes undue dyspnea or fatigue, chest pain, or near syncope. II) PH; ordinary physical activity slightly limited and causes undue dyspnea or fatigue, chest pain, or near syncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope; comfortable at rest. IV) PH; physical activity causes symptoms and increased discomfort; signs of right heart failure; dyspnea/fatigue possibly at rest. |
| A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Short Form 36 (SF-36) Health Survey Scale - Composite Physical Health | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Composite Mental Health | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Physical Functioning | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
| The Incidence of Confirmed Serum ALT or AST Concentrations > 5 x ULN That Were Related to Ambrisentan and Resulted in Discontinuation of Study Drug. | Week 12 | The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations \> 5 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in discontinuation of drug. Safety analysis set included all participants who received at least 1 dose of study drug. |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Bodily Pain | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - General Health | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Vitality | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Social Functioning | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Emotional | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Mental Health | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
| Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Physical | Baseline to Week 12 | The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ambrisentan All eligible subjects received 2.5 mg ambrisentan once daily for a period of 4 weeks before increasing the dose to 5 mg once daily. After Week 24, investigators were allowed to adjust the dose of ambrisentan as clinically indicated (available doses were 2.5, 5, and 10 mg). | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event (post Week 12) | 5 |
| Overall Study | Adverse Event (through Week 12) | 2 |
Baseline characteristics
| Characteristic | Ambrisentan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age Continuous | 57.2 years STANDARD_DEVIATION 13.39 |
| Baseline 6-Minute Walk Distance | 397.2 meters STANDARD_DEVIATION 104.59 |
| Body Mass Index | 27.2 kg/m^2 STANDARD_DEVIATION 5.44 |
| Borg dyspnea index | 4.2 units on a scale STANDARD_DEVIATION 2.31 |
| Cardiac index | 2.7 L/min/m^2 STANDARD_DEVIATION 1.02 |
| Height | 165.1 cm STANDARD_DEVIATION 7.22 |
| Mean pulmonary artery pressure | 48.4 mmHg STANDARD_DEVIATION 13.5 |
| Pulmonary Arterial Hypertension Etiology Associated pulmonary arterial hypertension | 12 participants |
| Pulmonary Arterial Hypertension Etiology Familial pulmonary arterial hypertension | 1 participants |
| Pulmonary Arterial Hypertension Etiology Idiopathic pulmonary arterial hypertension | 23 participants |
| Pulmonary arterial hypertension present | 3.8 year STANDARD_DEVIATION 4.99 |
| Pulmonary Arterial Hypertension Treatment Ambrisentan only | 11 participants |
| Pulmonary Arterial Hypertension Treatment Ambrisentan/prostanoid | 8 participants |
| Pulmonary Arterial Hypertension Treatment Ambrisentan/sildenafil | 12 participants |
| Pulmonary Arterial Hypertension Treatment Ambrisentan/sildenafil/prostanoid | 5 participants |
| Pulmonary capillary wedge pressure | 10.1 mmHg STANDARD_DEVIATION 5.38 |
| Pulmonary vascular resistance | 10.3 mmHg/L/min STANDARD_DEVIATION 5.75 |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized Black | 2 participants |
| Race/Ethnicity, Customized Caucasian | 28 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Region of Enrollment Australia | 5 participants |
| Region of Enrollment Belgium | 2 participants |
| Region of Enrollment Netherlands | 3 participants |
| Region of Enrollment United States | 26 participants |
| Right atrial pressure | 7.9 mmHg STANDARD_DEVIATION 5.29 |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight | 74.1 kg STANDARD_DEVIATION 15.36 |
| World Health Organization (WHO) Functional Class Class I | 0 participants |
| World Health Organization (WHO) Functional Class Class II | 13 participants |
| World Health Organization (WHO) Functional Class Class III | 23 participants |
| World Health Organization (WHO) Functional Class Class IV | 0 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 17 / 36 |
Outcome results
Primary
The Incidence of Confirmed Serum Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Concentrations > 3 x the Upper Limit of Normal (ULN) Considered to be Related to Ambrisentan and Resulted in Discontinuation of Study Drug.
The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations \> 3 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in discontinuation of study drug. Safety analysis set included all participants who received at least 1 dose of study drug.
Time frame: Week 12
Population: The Safety analysis set was defined as all subjects who received at least 1 dose of study drug. All subjects who received at least 1 dose of ambrisentan were followed (to the extent possible) to the end of the study and included in the analyses of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ambrisentan | The Incidence of Confirmed Serum Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Concentrations > 3 x the Upper Limit of Normal (ULN) Considered to be Related to Ambrisentan and Resulted in Discontinuation of Study Drug. | 0 Participants |
Comparison: Sample size: 30 participants; 80% power to rule out 50% recurrence rate of serum ALT/AST abnormalities following ambrisentan treatment (assumes 25% recurrence rate); 99% power to rule out 75% recurrence rate (assumes 37.5% recurrence rate). H\_0 = proportion of subjects experiencing primary endpoint at 12% vs 1-sided alternative of \< 12%. P-value from exact binomial test. Summary statistics included the estimated proportion, 95% confidence interval (CI), and the p-value of the hypothesis test.p-value: 0.0195% CI: [0, 9.7]Exact binomial test
Secondary
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Borg Dyspnea Index Immediately Following Exercise
Change from baseline evaluated after 12 weeks of ambrisentan therapy in Borg dyspnea index (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Borg Dyspnea Index Immediately Following Exercise | -0.5 Units on a scale | Standard Deviation 1.51 |
Comparison: Hypothesis testing and descriptive statistics were carried out on the last-observation-carried-forward (LOCF) Borg dyspnea index change from baseline.p-value: 0.04695% CI: [-1, 0]t-test, 2 sided
Secondary
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Short Form 36 (SF-36) Health Survey Scale - Composite Physical Health
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Short Form 36 (SF-36) Health Survey Scale - Composite Physical Health | 4.6 Units on a scale | Standard Deviation 6.44 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.00195% CI: [2.1, 7.1]t-test, 2 sided
Secondary
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in the 6-Minute Walk Distance Test (6MWD)
The 6MWD test is a measure of exercise tolerance, and measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface.
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in the 6-Minute Walk Distance Test (6MWD) | 23.4 meters | Standard Deviation 49.6 |
Comparison: Hypothesis testing and descriptive statistics were carried out on the last-observation-carried-forward (LOCF) 6-minute walk distance change from baseline.p-value: 0.00995% CI: [6.3, 40.4]t-test, 2 sided
Secondary
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class
Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes undue dyspnea or fatigue, chest pain, or near syncope. II) PH; ordinary physical activity slightly limited and causes undue dyspnea or fatigue, chest pain, or near syncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope; comfortable at rest. IV) PH; physical activity causes symptoms and increased discomfort; signs of right heart failure; dyspnea/fatigue possibly at rest.
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan | A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class | Improved | 15 Participants |
| Ambrisentan | A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class | No Change | 18 Participants |
| Ambrisentan | A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class | Deteriorated | 2 Participants |
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Bodily Pain
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Bodily Pain | 3.1 Units on a scale | Standard Deviation 6.4 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.01795% CI: [0.6, 5.6]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Composite Mental Health
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Composite Mental Health | 3.4 Units on a scale | Standard Deviation 8.98 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.05995% CI: [-0.1, 6.8]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - General Health
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - General Health | 3.0 Units on a scale | Standard Deviation 7.45 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.04695% CI: [0.1, 5.8]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Mental Health
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Mental Health | 3.9 Units on a scale | Standard Deviation 5.78 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.00195% CI: [1.7, 6.2]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Physical Functioning
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Physical Functioning | 4.4 Units on a scale | Standard Deviation 6.86 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.00295% CI: [1.7, 7]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Emotional
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Emotional | 3.9 Units on a scale | Standard Deviation 13.96 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.15295% CI: [-1.5, 9.3]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Physical
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Physical | 7.2 Units on a scale | Standard Deviation 10.56 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.00195% CI: [3.1, 11.3]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Social Functioning
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Social Functioning | 3.5 Units on a scale | Standard Deviation 9.41 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.05995% CI: [-0.1, 7.2]t-test, 2 sided
Secondary
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Vitality
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Time frame: Baseline to Week 12
Population: The Intention-to-Treat (ITT) analysis set was defined as all subjects who received at least 1 dose of study drug and had at least 1 postdose efficacy value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Vitality | 4.5 Units on a scale | Standard Deviation 7.23 |
Comparison: Seven subjects were evaluated by the incorrect version of the SF-36 questionnaire at the baseline visit and were not included in the analysis; therefore n = 28 for mean baseline scores, and n = 28 for mean change from baseline at Week 12.p-value: 0.00395% CI: [1.7, 7.3]t-test, 2 sided
Secondary
The Incidence of Confirmed Serum ALT or AST Concentrations > 3 x ULN That Were Related to Ambrisentan and Resulted in Dose Reduction
The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations \> 3 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in dose reduction. Safety analysis set included all participants who received at least 1 dose of study drug.
Time frame: Week 12
Population: The Safety analysis set was defined as all subjects who received at least 1 dose of study drug. All subjects who received at least 1 dose of ambrisentan were followed (to the extent possible) to the end of the study and included in the analyses of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ambrisentan | The Incidence of Confirmed Serum ALT or AST Concentrations > 3 x ULN That Were Related to Ambrisentan and Resulted in Dose Reduction | 0 participants |
Secondary
The Incidence of Confirmed Serum ALT or AST Concentrations > 5 x ULN That Were Related to Ambrisentan and Resulted in Discontinuation of Study Drug.
The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations \> 5 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in discontinuation of drug. Safety analysis set included all participants who received at least 1 dose of study drug.
Time frame: Week 12
Population: The Safety analysis set was defined as all subjects who received at least 1 dose of study drug. All subjects who received at least 1 dose of ambrisentan were followed (to the extent possible) to the end of the study and included in the analyses of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ambrisentan | The Incidence of Confirmed Serum ALT or AST Concentrations > 5 x ULN That Were Related to Ambrisentan and Resulted in Discontinuation of Study Drug. | 0 participants |