Trial Outcomes & Findings for Efficacy Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH) (NCT NCT01808313)

NCT ID: NCT01808313

Last Updated: 2017-06-06

Results Overview

The 6MWT measures the distance that a participant can walk in a period of 6 minutes. Change from Baseline was calculated as the Week 12 value minus the Baseline value. Baseline 6MWT comprised of an average of the last two consecutive measurements prior to dosing that varied by not greater than 10 percent (%). If only one measurement was available, that measurement was used as the Baseline value. The last observation carried forward method was used to impute missing values.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 134 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2017-06-06

Participant Flow

A total of 134 participants were enrolled and received at least one dose of study medication. 133 participants comprised the Intent-to-Treat (ITT) Population (all participants that received at least one dose of study treatment and had an efficacy assessment performed both at Baseline and after administration of the study treatment).

Participant milestones

Measure	Ambrisentan Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Overall Study STARTED	133
Overall Study COMPLETED	123
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	Ambrisentan Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Overall Study Adverse Event	5
Overall Study Protocol Violation	2
Overall Study Met Protocol-defined Stopping Criteria	1
Overall Study Lost to Follow-up	1
Overall Study Physician Decision	1

Baseline Characteristics

Efficacy Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)

Baseline characteristics by cohort

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Age, Continuous	36.1 Years STANDARD_DEVIATION 10.25 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	133 Particiopants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-Treat (ITT) Population: all participants who received at least one dose of study medication and had an efficacy assessment performed both at Baseline and after administration of the study medication

The 6MWT measures the distance that a participant can walk in a period of 6 minutes. Change from Baseline was calculated as the Week 12 value minus the Baseline value. Baseline 6MWT comprised of an average of the last two consecutive measurements prior to dosing that varied by not greater than 10 percent (%). If only one measurement was available, that measurement was used as the Baseline value. The last observation carried forward method was used to impute missing values.

Outcome measures

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in 6-minutes Walk Test (6MWT) at Week 12	53.59 Meters Standard Deviation 64.494

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population.

The 6MWT measures the distance that a participant can walk in a period of 6 minutes. Change from Baseline was calculated as the Week 24 value minus the Baseline value. Baseline 6MWT comprised of an average of the last two consecutive measurements prior to dosing that varied by not greater than 10%. If only one measurement was available, that measurement was used as the Baseline value. The last observation carried forward method was used to impute missing values.

Outcome measures

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in 6MWT at Week 24	64.36 Meters Standard Deviation 91.173

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT Population

The WHO FC was determined by the investigator as follows: Class I- Participants with pulmonary hypertension (PH) but without resulting limitation of physical activity, II- Participants with PH resulting in slight limitation of physical activity, III- Participants with PH resulting in marked limitation of physical activity, IV- Participants with PH with inability to carry out any physical activity without symptoms. Changes from Baseline in functional class were summarized at Weeks 12 and 24. The number of participants improving by 2 classes, improving by 1 class, not changing, worsening by 1 class or worsening by 2 classes from Baseline at Weeks 12 and 24 were evaluated. The Baseline value was the last non-missing assessment value before treatment. Only participants with non-missing Baseline values and at least one non-missing post-Baseline value of the response variable were included. The last observation carried forward method was used to impute missing values.

Outcome measures

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Improved by 2 classes at Week 12	0 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Improved by 1 class at Week 12	44 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Not changing at Week 12	84 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Worsened by 1 class at Week 12	4 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Worsened by 2 classes at Week 12	1 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Improved by 2 classes at Week 24	0 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Improved by 1 class at Week 24	51 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Not changing at Week 24	77 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Worsened by 1 class at Week 24	3 Participants
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 Worsened by 2 classes at Week 24	2 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT Population.

The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum). Change from Baseline was calculated as the Week 12 and 24 values minus the Baseline values. The BDI indicates the degree of exertion, breathlessness, fatigue, or difficulty breathing after completion of the 6MWT. The lower values, 0 as the lowest, indicates no exertion, fatigue, or breathlessness felt, and 10 would be the maximum amount of exertion felt as assessed by each participant. The last observation carried forward method was used to impute missing values.

Outcome measures

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 Week 12	-0.34 scores on a scale Standard Deviation 1.521
Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 Week 24	-0.22 scores on a scale Standard Deviation 1.952

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by number of participants \[n\]=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflect everyone in the ITT Population.

N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) is a surrogate maker of heart failure and was measured by a central laboratory. Mean change from Baseline at Weeks 12 and 24 were calculated as the Weeks 12 and 24 values minus the Baseline values.Observed data was analyzed (no imputation technique was performed for missing data). Log transformed mean change from Baseline at Weeks 12 and 24 data are summarized.

Outcome measures

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Weeks 12 and 24 Week 12, n=123	0.44 log(ng/L) Standard Deviation 2.687
Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Weeks 12 and 24 Week 24, n=122	0.37 log(ng/L) Standard Deviation 3.103

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population: This population comprised of all participants who received at least one dose of study medication.

Time to clinical worsening is defined as the time from Baseline to the first occurrence of death, lung transplantation, hospitalization for PAH treatment, atrial septostomy, or Investigational product (IP) discontinuation (discon) due to change to other PAH treatment. Time to clinical worsening was measured as the number of participants who experienced these events during 12 and 24 Weeks.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Death at Week 12	2 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Lung Transplant at Week 12	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Hospitalization for PAH at Week 12	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Atrial Septostomy at Week 12	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event IP discon (additional medication) at Week 12	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Death at Week 24	3 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Lung Transplant at Week 24	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Hospitalization for PAH at Week 24	1 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event Atrial Septostomy at Week 24	0 Participants
Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event IP discon (additional medication) at Week 24	0 Participants

SECONDARY outcome

Timeframe: From the start of study treatment up to Week 24

Population: Safety Population

An adverse event (AE) is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event (SAE) is 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/incapacity, a congenital anomaly/birth defect, or important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation Any AEs	91 Participants
Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation Any SAEs	11 Participants
Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation AEs leading to discontinuation	4 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: Safety Population

Complete physical examinations of each participant by the investigator were performed at the Screening Visit, Week 12 and Week 24 Visit/Early withdrawal visits. The physical examination included an examination of the following: general appearance, skin, head, ears, eyes, nose, throat, neck, thyroid, lymph nodes, cardiovascular system, respiratory system, abdomen, musculoskeletal system, neurological system and height. Physical examination summary results were not collected therefore there is no data to present for this outcome measure.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Number of Participants With Physical Examination Findings	NA Participants Summary data was not compiled for this outcome measure therefore there is no data to present.

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Heart rate was measured in order to monitor vital signs by the 12-lead ECG at Baseline, Weeks 12 and 24. Change from Baseline in ECG heart rate is summarized for each post-Baseline assessment at Weeks 12 and 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last non-missing observed value before treatment.

Outcome measures

Measure	Ambrisentan n=128 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Electrocardiogram (ECG) Heart Rate Values at Weeks 12 and 24 Week 12, n=124	-2.0 Beats per minute Standard Deviation 16.65
Change From Baseline in Electrocardiogram (ECG) Heart Rate Values at Weeks 12 and 24 Week 24, n=118	-4.6 Beats per minute Standard Deviation 14.68

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

The ECG parameters, PR interval, QRS duration, uncorrected QT interval, QTcB were measured at Baseline, Weeks 12 and 24. Change from Baseline in ECG heart rate is summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last non-missing observed value before treatment.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 PR interval, Week 12, n=122	0.7 Milliseconds Standard Deviation 16.55
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 PR interval, Week 24, n=117	1.5 Milliseconds Standard Deviation 14.84
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 QRS duration, Week 12, n=124	-1.5 Milliseconds Standard Deviation 15.84
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 QRS duration, Week 24, n=118	0.7 Milliseconds Standard Deviation 14.40
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 Uncorrected QT Interval, Week 12, n=124	-0.7 Milliseconds Standard Deviation 37.44
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 Uncorrected QT Interval, Week 24, n=118	6.8 Milliseconds Standard Deviation 40.41
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 Corrected QTcB interval, Week 12, n=123	-4.9 Milliseconds Standard Deviation 29.74
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 Corrected QTcB interval, Week 24, n=117	-1.5 Milliseconds Standard Deviation 37.25

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood pressure measurements (pre-6MWT and post-6MWT) were taken to monitor vital signs and included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the Baseline, Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in SBP and DBP were summarized for each post-Baseline assessment upto Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last non-missing observed value before treatment.

Outcome measures

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; pre-6MWT; Week 4; n=131	-1.6 Millimeters of mercury (mmHg) Standard Deviation 11.57
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; post-6MWT; Week 4; n=131	0.7 Millimeters of mercury (mmHg) Standard Deviation 15.36
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; pre-6MWT; Week 8; n=126	-2.2 Millimeters of mercury (mmHg) Standard Deviation 13.89
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; post-6MWT, Week 8; n=126	2.3 Millimeters of mercury (mmHg) Standard Deviation 17.36
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; pre-6MWT; Week 12; n=126	-1.9 Millimeters of mercury (mmHg) Standard Deviation 15.08
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; post-6MWT; Week 12; n=125	0.3 Millimeters of mercury (mmHg) Standard Deviation 18.23
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; pre-6MWT; Week 16; n=124	-1.8 Millimeters of mercury (mmHg) Standard Deviation 14.55
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; post-6MWT; Week 16; n=123	1.7 Millimeters of mercury (mmHg) Standard Deviation 17.71
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; pre-6MWT; Week 20; n=122	-3.3 Millimeters of mercury (mmHg) Standard Deviation 14.42
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; post-6MWT, Week 20; n=122	1.3 Millimeters of mercury (mmHg) Standard Deviation 18.07
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; pre-6MWT; Week 24; n=123	-3.4 Millimeters of mercury (mmHg) Standard Deviation 15.14
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 SBP; post-6MWT; Week 24; n=123	1.0 Millimeters of mercury (mmHg) Standard Deviation 19.01
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; pre-6MWT; Week 4; n=131	-3.2 Millimeters of mercury (mmHg) Standard Deviation 9.30
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; post-6MWT; Week 4; n=131	-1.6 Millimeters of mercury (mmHg) Standard Deviation 11.19
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; pre-6MWT; Week 8; n=126	-3.6 Millimeters of mercury (mmHg) Standard Deviation 9.73
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; post-6MWT; Week 8; n=126	-1.8 Millimeters of mercury (mmHg) Standard Deviation 11.48
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; pre-6MWT; Week 12; n=126	-3.5 Millimeters of mercury (mmHg) Standard Deviation 10.39
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; post-6MWT; Week 12; n=125	-4.2 Millimeters of mercury (mmHg) Standard Deviation 12.84
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; pre-6MWT; Week 16; n=124	-5.0 Millimeters of mercury (mmHg) Standard Deviation 11.66
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; post-6MWT; Week 16; n=123	-3.0 Millimeters of mercury (mmHg) Standard Deviation 14.20
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; pre-6MWT; Week 20; n=122	-4.6 Millimeters of mercury (mmHg) Standard Deviation 10.97
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; post-6MWT; Week 20; n=122	-2.5 Millimeters of mercury (mmHg) Standard Deviation 14.37
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; pre-6MWT; Week 24; n=123	-4.6 Millimeters of mercury (mmHg) Standard Deviation 12.35
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 DBP; post-6MWT; Week 24; n=123	-2.5 Millimeters of mercury (mmHg) Standard Deviation 13.30

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Vital sign monitoring included heart rate measurements at (pre-6MWT and post-6MWT at the Baseline visit, Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last non-missing value observed before treatment. At Baseline, Weeks 12 and 28, heart rate was recorded at the end of the 6MWT and at 1 minute (M), 2 M and 3 M, after completion of the 6MWT with the participants seated, and the time that heart rate recovered to the level of pre-6MWT.

Outcome measures

Measure	Ambrisentan n=133 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; pre-6MWT; Week 4; n=131	-0.7 Beats per minute Standard Deviation 12.12
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT; Week 4; n=131	-2.1 Beats per minute Standard Deviation 18.26
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; pre-6MWT; Week 8; n=126	-1.2 Beats per minute Standard Deviation 13.10
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT, Week 8; n=126	-0.2 Beats per minute Standard Deviation 17.39
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; pre-6MWT; Week 12; n=126	-1.7 Beats per minute Standard Deviation 12.27
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT; Week 12; n=124	0.6 Beats per minute Standard Deviation 18.23
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT 1M; Week 12; n=124	-0.9 Beats per minute Standard Deviation 15.11
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT 2 M; Week 12; n=124	-2.2 Beats per minute Standard Deviation 13.51
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT 3 M; Week 12; n=125	-1.2 Beats per minute Standard Deviation 13.90
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; Recovery to Pre-6MWT; Week 12; n=125	-1.5 Beats per minute Standard Deviation 12.50
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; pre-6MWT; Week 16; n=124	-2.6 Beats per minute Standard Deviation 13.10
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT; Week 16; n=123	0.5 Beats per minute Standard Deviation 19.81
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; pre-6MWT; Week 20; n=122	-3.6 Beats per minute Standard Deviation 12.45
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT, Week 20; n=122	0.4 Beats per minute Standard Deviation 20.82
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; pre-6MWT; Week 24; n=123	-0.8 Beats per minute Standard Deviation 13.34
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT; Week 24; n=123	3.4 Beats per minute Standard Deviation 21.88
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT 1 M; Week 24; n=121	0.3 Beats per minute Standard Deviation 16.57
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT 2 M; Week 24; n=121	-0.5 Beats per minute Standard Deviation 13.95
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; post-6MWT 3 M; Week 24; n=122	-0.2 Beats per minute Standard Deviation 13.41
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 Heart Rate; Recovery to Pre-6MWT; Week 24; n=123	-0.4 Beats per minute Standard Deviation 13.39

SECONDARY outcome

Timeframe: Baseline

Population: Safety Population

Oral temperature was used to monitor vital signs and collected at the Screening visit.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Oral Temperature	36.4 Celsius Interval 35.0 to 37.3

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of ALT, ALP, AST and BILT at the Baseline visit and up to Week 24. Shift from Baseline (BL) was calculated as the individual maximum of post-BL value minus the BL value. The BL value is defined as the last pre-treatment value observed. Threshold values for the liver function test results, which were considered as potential values of clinical concern, were 3 times the upper limit of normal (ULN) for ALT, AST and ALP and 2 times the ULN for BILT. Maximum liver function abnormal values of post-BL are summarized.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 ALT; BL <=1 x ULN shift to >3 x ULN post-BL;n=133	0 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 ALT; >1 x - <3 x ULN shift to >3 x ULN; n=133	3 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 ALP; <=1 x ULN shift to >3 x ULN; n=132	0 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 ALP; >1 x - <3 x ULN shift to >3 x ULN; n=132	0 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 AST; <=1 x ULN shift to >3 x ULN; n=133	0 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 AST; >1 x - <3 x ULN shift to >3 x ULN; n=133	2 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 BILT; >1 x - <2 x ULN shift to >2 x ULN; n=133	1 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 BILT; >1 x - <3 x ULN shift to >2 x ULN; n=133	3 Participants
Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 BILT; >1 x - >2 x ULN shift to >2 x ULN; n=133	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and WBC count at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and WBC count values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Eosinophils; Week 8; n=125	-0.0004 Giga cells per liter Standard Deviation 0.0588
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Eosinophils; Week 12; n=125	0.0012 Giga cells per liter Standard Deviation 0.0603
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Eosinophils; Week 16; n=125	0.0126 Giga cells per liter Standard Deviation 0.1466
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Eosinophils; Week 20; n=125	0.0014 Giga cells per liter Standard Deviation 0.0582
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Eosinophils; Week 24; n=123	0.0014 Giga cells per liter Standard Deviation 0.0854
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Lymphocytes; Week 4; n=133	-0.257 Giga cells per liter Standard Deviation 0.5558
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Lymphocytes; Week 8; n=125	-0.201 Giga cells per liter Standard Deviation 0.6116
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Lymphocytes; Week 12; n=125	-0.284 Giga cells per liter Standard Deviation 0.5743
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Lymphocytes; Week 16; n=125	-0.295 Giga cells per liter Standard Deviation 0.5821
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Lymphocytes; Week 20; n=125	-0.378 Giga cells per liter Standard Deviation 0.6600
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Lymphocytes; Week 24; n=123	-0.363 Giga cells per liter Standard Deviation 0.6897
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Monocytes; Week 4; n=133	-0.011 Giga cells per liter Standard Deviation 0.1684
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Monocytes; Week 8; n=125	-0.013 Giga cells per liter Standard Deviation 0.1713
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Monocytes; Week 12; n=125	-0.032 Giga cells per liter Standard Deviation 0.1659
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Monocytes; Week 16; n=125	-0.019 Giga cells per liter Standard Deviation 0.1665
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Monocytes; Week 20; n=125	-0.044 Giga cells per liter Standard Deviation 0.1574
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Monocytes; Week 24; n=123	-0.000 Giga cells per liter Standard Deviation 0.4885
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Total Neutrophils; Week 4; n=133	-0.4093 Giga cells per liter Standard Deviation 1.7597
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Total Neutrophils; Week 8; n=125	-0.4209 Giga cells per liter Standard Deviation 1.8660
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Total Neutrophils; Week 12; n=125	-0.5958 Giga cells per liter Standard Deviation 1.8947
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Total Neutrophils; Week 16; n=125	-0.7201 Giga cells per liter Standard Deviation 2.1282
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Total Neutrophils; Week 20; n=125	-0.9510 Giga cells per liter Standard Deviation 2.0706
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Total Neutrophils; Week 24; n=123	-0.9247 Giga cells per liter Standard Deviation 2.2646
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Platelet Count; Week 4; n=133	-4.80 Giga cells per liter Standard Deviation 41.562
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Platelet Count; Week 8; n=125	-3.00 Giga cells per liter Standard Deviation 49.357
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Platelet Count; Week 12; n=125	-1.56 Giga cells per liter Standard Deviation 54.690
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Platelet Count; Week 16; n=125	-6.04 Giga cells per liter Standard Deviation 50.227
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Platelet Count; Week 20; n=125	-7.89 Giga cells per liter Standard Deviation 52.007
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Platelet Count; Week 24; n=123	-4.75 Giga cells per liter Standard Deviation 45.181
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 WBC Count; Week 4; n=133	-0.689 Giga cells per liter Standard Deviation 1.9433
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 WBC count; Week 8; n=125	-0.642 Giga cells per liter Standard Deviation 2.1480
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 WBC count; Week 12; n=125	-0.925 Giga cells per liter Standard Deviation 2.1708
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 WBC Count; Week 16; n=125	-1.050 Giga cells per liter Standard Deviation 2.3951
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 WBC count; Week 20; n=125	-1.387 Giga cells per liter Standard Deviation 2.2706
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 WBC count; Week 24; n=123	-1.342 Giga cells per liter Standard Deviation 2.5167
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Basophils; Week 4; n=133	-0.010 Giga cells per liter Standard Deviation 0.0434
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Basophils; Week 8; n=125	-0.007 Giga cells per liter Standard Deviation 0.0479
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Basophils; Week12; n=125	-0.009 Giga cells per liter Standard Deviation 0.0438
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Basophils; Week 16; n=125	-0.006 Giga cells per liter Standard Deviation 0.0484
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Basophils; Week 20; n=125	-0.002 Giga cells per liter Standard Deviation 0.0366
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Basophils; Week 24; n=123	-0.002 Giga cells per liter Standard Deviation 0.0792
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 Eosinophils; Week 4; n=133	-0.0077 Giga cells per liter Standard Deviation 0.0515

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of hemoglobin at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the hemoglobin count values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 Hemoglobin; Week 4; n=133	-7.46 Grams per liter Standard Deviation 11.345
Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 Hemoglobin; Week 8; n=125	-6.80 Grams per liter Standard Deviation 13.642
Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 Hemoglobin; Week12; n=125	-6.29 Grams per liter Standard Deviation 14.269
Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 Hemoglobin; Week 16; n=125	-6.87 Grams per liter Standard Deviation 14.245
Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 Hemoglobin; Week 20; n=125	-8.19 Grams per liter Standard Deviation 14.862
Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 Hemoglobin; Week 24; n=123	-6.56 Grams per liter Standard Deviation 14.724

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of hematocrit at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the hematocrit values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is defined as the last Pre-treatment value observed. The unit of measure is defined as the proprtion of red blood cells in blood.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 Hematocrit; Week 4; n=133	-0.0168 Proportion of 1 Standard Deviation 0.0587
Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 Hematocrit; Week 8; n=125	-0.0209 Proportion of 1 Standard Deviation 0.0412
Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 Hematocrit; Week12; n=125	-0.0180 Proportion of 1 Standard Deviation 0.0420
Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 Hematocrit; Week 16; n=125	-0.0179 Proportion of 1 Standard Deviation 0.0443
Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 Hematocrit; Week 20; n=125	-0.0220 Proportion of 1 Standard Deviation 0.0459
Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 Hematocrit; Week 24; n=123	-0.0176 Proportion of 1 Standard Deviation 0.0422

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of mean corpuscle hemoglobin at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the hemoglobin values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 Mean Corpuscle Hemoglobin; Week 4; n=133	0.258 Picogram Standard Deviation 1.4064
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 Mean Corpuscle Hemoglobin; Week 8; n=125	0.405 Picogram Standard Deviation 1.5405
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 Mean Corpuscle Hemoglobin; Week12; n=125	0.347 Picogram Standard Deviation 2.1082
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 Mean Corpuscle Hemoglobin; Week 16; n=125	0.185 Picogram Standard Deviation 2.0053
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 Mean Corpuscle Hemoglobin; Week 20; n=125	0.019 Picogram Standard Deviation 2.0040
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 Mean Corpuscle Hemoglobin; Week 24; n=123	-0.035 Picogram Standard Deviation 2.0831

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of mean corpuscle volume at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the mean corpuscle volume values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 Mean corpuscle volume; Week 4; n=133	0.906 Femtoliters Standard Deviation 2.8849
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 Mean corpuscle volume; Week 8; n=125	1.362 Femtoliters Standard Deviation 3.8958
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 Mean corpuscle volume; Week12; n=125	0.485 Femtoliters Standard Deviation 7.4220
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 Mean corpuscle volume; Week 16; n=125	0.725 Femtoliters Standard Deviation 6.6333
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 Mean corpuscle volume; Week 20; n=125	0.587 Femtoliters Standard Deviation 4.7209
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 Mean corpuscle volume; Week 24; n=123	0.392 Femtoliters Standard Deviation 4.8609

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of RBC count at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the red blood cell count values were summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 RBC count; Week 4; n=133	-0.2773 Trillion cells per liter Standard Deviation 0.3678
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 RBC count; Week 8; n=125	-0.2987 Trillion cells per liter Standard Deviation 0.4781
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 RBC count; Week12; n=125	-0.2520 Trillion cells per liter Standard Deviation 0.4672
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 RBC count; Week 16; n=125	-0.2595 Trillion cells per liter Standard Deviation 0.5066
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 RBC count; Week 20; n=125	-0.2733 Trillion cells per liter Standard Deviation 0.5414
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 RBC count; Week 24; n=123	-0.2182 Trillion cells per liter Standard Deviation 0.4802

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of albumin, globulin and total protein at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the albumin, globulin and total protein values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Albumin; Week 4; n=132	1.01 Grams per liter Standard Deviation 4.274
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Albumin; Week 8; n=126	1.09 Grams per liter Standard Deviation 3.717
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Albumin; Week12; n=126	1.09 Grams per liter Standard Deviation 4.105
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Albumin; Week 16; n=126	1.05 Grams per liter Standard Deviation 4.098
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Albumin; Week 20; n=121	0.64 Grams per liter Standard Deviation 4.625
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Albumin; Week 24; n=120	1.31 Grams per liter Standard Deviation 4.390
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Globulin; Week 4; n=112	-1.63 Grams per liter Standard Deviation 5.083
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Globulin; Week 8; n=106	-2.17 Grams per liter Standard Deviation 6.083
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Globulin; Week12; n=107	-2.38 Grams per liter Standard Deviation 6.456
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Globulin; Week 16; n=107	-2.24 Grams per liter Standard Deviation 6.120
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Globulin; Week 20; n=103	-2.57 Grams per liter Standard Deviation 6.126
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Globulin; Week 24; n=103	-2.25 Grams per liter Standard Deviation 6.251
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Total Protein; Week 4; n=132	-1.19 Grams per liter Standard Deviation 9.058
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Total Protein; Week 8; n=127	-1.25 Grams per liter Standard Deviation 8.555
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Total Protein; Week12; n=126	-1.57 Grams per liter Standard Deviation 8.835
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Total Protein; Week 16; n=126	-1.37 Grams per liter Standard Deviation 7.854
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Total Protein; Week 20; n=122	-2.60 Grams per liter Standard Deviation 10.129
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 Total Protein; Week 24; n=121	-0.91 Grams per liter Standard Deviation 8.841

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), creatine kinase (CK), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the ALP, ALT, AST, CK, GGT and LDH values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALP; Week 4; n=131	-4.20 International units per liter Standard Deviation 14.945
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALP; Week 8; n=124	-6.19 International units per liter Standard Deviation 16.612
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALP; Week12; n=125	-6.79 International units per liter Standard Deviation 16.815
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALP; Week 16; n=122	-4.47 International units per liter Standard Deviation 18.916
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALP; Week 20; n=124	-5.99 International units per liter Standard Deviation 18.255
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALP; Week 24; n=121	-2.95 International units per liter Standard Deviation 23.104
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALT; Week 4; n=133	0.07 International units per liter Standard Deviation 20.479
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALT; Week 8; n=127	-1.58 International units per liter Standard Deviation 20.411
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALT; Week12; n=127	-5.69 International units per liter Standard Deviation 16.770
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALT; Week 16; n=126	-5.33 International units per liter Standard Deviation 16.064
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALT; Week 20; n=125	-5.44 International units per liter Standard Deviation 19.143
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 ALT; Week 24; n=123	-5.62 International units per liter Standard Deviation 15.734
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 AST; Week 4; n=132	0.18 International units per liter Standard Deviation 24.671
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 AST; Week 8; n=127	-1.55 International units per liter Standard Deviation 13.848
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 AST; Week12; n=127	-3.51 International units per liter Standard Deviation 13.835
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 AST; Week 16; n=125	-4.03 International units per liter Standard Deviation 12.710
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 AST; Week 20; n=125	-3.80 International units per liter Standard Deviation 15.021
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 AST; Week 24; n=123	-3.63 International units per liter Standard Deviation 12.091
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 CK; Week 4; n=129	-1.78 International units per liter Standard Deviation 35.099
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 CK; Week 8; n=123	11.21 International units per liter Standard Deviation 182.414
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 CK; Week12; n=124	1.62 International units per liter Standard Deviation 105.342
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 CK; Week 16; n=121	0.07 International units per liter Standard Deviation 100.783
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 CK; Week 20; n=120	-1.79 International units per liter Standard Deviation 86.528
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 CK; Week 24; n=116	0.32 International units per liter Standard Deviation 89.377
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 GGT; Week 4; n=131	-4.67 International units per liter Standard Deviation 46.013
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 GGT; Week 8; n=127	-10.91 International units per liter Standard Deviation 49.174
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 GGT; Week12; n=127	-15.82 International units per liter Standard Deviation 52.509
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 GGT; Week 16; n=124	-13.98 International units per liter Standard Deviation 55.130
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 GGT; Week 20; n=125	-20.42 International units per liter Standard Deviation 58.287
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 GGT; Week 24; n=122	-21.84 International units per liter Standard Deviation 56.557
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 LDH; Week 4; n=122	-20.45 International units per liter Standard Deviation 53.720
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 LDH; Week 8; n=118	-19.24 International units per liter Standard Deviation 80.068
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 LDH; Week12; n=118	-28.15 International units per liter Standard Deviation 77.867
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 LDH; Week 16; n=117	-29.37 International units per liter Standard Deviation 82.565
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 LDH; Week 20; n=117	-26.65 International units per liter Standard Deviation 81.007
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 LDH; Week 24; n=113	-27.38 International units per liter Standard Deviation 74.551

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of direct bilirubin, total bilirubin, creatinine and uric acid at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the direct bilirubin, total bilirubin, creatinine and uric acid values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Direct Bilirubin; Week 4; n=131	-0.326 Micromoles per liter Standard Deviation 2.0821
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Direct Bilirubin; Week 8; n=126	-0.538 Micromoles per liter Standard Deviation 2.5429
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Direct Bilirubin; Week12; n=127	-0.787 Micromoles per liter Standard Deviation 2.5038
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Direct Bilirubin; Week 16; n=126	-0.778 Micromoles per liter Standard Deviation 2.7692
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Direct Bilirubin; Week 20; n=125	-0.780 Micromoles per liter Standard Deviation 2.5072
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Direct Bilirubin; Week 24; n=122	-0.752 Micromoles per liter Standard Deviation 2.7299
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Total Bilirubin; Week 4; n=131	-0.72 Micromoles per liter Standard Deviation 5.903
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Total Bilirubin; Week 8; n=127	-1.12 Micromoles per liter Standard Deviation 6.089
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Total Bilirubin; Week12; n=127	-0.49 Micromoles per liter Standard Deviation 17.178
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Total Bilirubin; Week 16; n=126	-1.49 Micromoles per liter Standard Deviation 6.866
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Total Bilirubin; Week 20; n=125	-1.65 Micromoles per liter Standard Deviation 6.329
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Total Bilirubin; Week 24; n=123	-1.25 Micromoles per liter Standard Deviation 6.927
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Creatinine; Week 4; n=133	-1.924 Micromoles per liter Standard Deviation 10.1256
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Creatinine; Week 8; n=127	-1.968 Micromoles per liter Standard Deviation 10.7823
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Creatinine; Week12; n=127	-0.759 Micromoles per liter Standard Deviation 9.2949
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Creatinine; Week 16; n=126	-0.847 Micromoles per liter Standard Deviation 10.0814
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Creatinine; Week 20; n=125	-0.970 Micromoles per liter Standard Deviation 9.3502
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Creatinine; Week 24; n=123	-0.217 Micromoles per liter Standard Deviation 9.9447
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Uric Acid; Week 4; n=129	-13.289 Micromoles per liter Standard Deviation 82.7246
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Uric Acid; Week 8; n=125	-13.159 Micromoles per liter Standard Deviation 87.0456
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Uric Acid; Week12; n=125	-16.580 Micromoles per liter Standard Deviation 83.7145
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Uric Acid; Week 16; n=124	-16.149 Micromoles per liter Standard Deviation 87.9857
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Uric Acid; Week 20; n=119	-24.584 Micromoles per liter Standard Deviation 94.9378
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 Uric Acid; Week 24; n=121	-13.168 Micromoles per liter Standard Deviation 95.0694

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Blood samples were collected for the measurement of calcium, cholesterol, chloride, glucose, potassium, magnesium, sodium, inorganic phosphorus, triglycerides and urea/Bun at the Baseline visit and Weeks 4, 8, 12, 16, 20 and 24. Change from Baseline in the calcium, cholesterol, chloride, glucose, potassium, magnesium, sodium, inorganic phosphorus, triglycerides and urea/BUN values were summarized for each post-Baseline assessment until Week 24. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Calcium; Week 4; n=132	-0.009 Millimoles per liter Standard Deviation 0.1321
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Calcium; Week 8; n=127	-0.020 Millimoles per liter Standard Deviation 0.1386
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Calcium; Week12; n=127	-0.008 Millimoles per liter Standard Deviation 0.1340
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Calcium; Week 16; n=126	-0.015 Millimoles per liter Standard Deviation 0.1470
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Calcium; Week 20; n=124	-0.006 Millimoles per liter Standard Deviation 0.1513
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Calcium; Week 24; n=123	0.007 Millimoles per liter Standard Deviation 0.1440
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Cholesterol; Week 4; n=132	-0.034 Millimoles per liter Standard Deviation 0.7416
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Cholesterol; Week 8; n=126	-0.062 Millimoles per liter Standard Deviation 0.8776
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Cholesterol; Week12; n=126	-0.180 Millimoles per liter Standard Deviation 0.9450
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Cholesterol; Week 16; n=126	-0.281 Millimoles per liter Standard Deviation 0.8570
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Cholesterol; Week 20; n=125	-0.277 Millimoles per liter Standard Deviation 0.8482
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Cholesterol; Week 24; n=121	-0.253 Millimoles per liter Standard Deviation 0.8340
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Chloride; Week 4; n=131	0.48 Millimoles per liter Standard Deviation 7.594
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Chloride; Week 8; n=127	1.02 Millimoles per liter Standard Deviation 3.858
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Chloride; Week12; n=127	1.51 Millimoles per liter Standard Deviation 3.409
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Chloride; Week 16; n=126	1.01 Millimoles per liter Standard Deviation 3.995
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Chloride; Week 20; n=124	1.40 Millimoles per liter Standard Deviation 3.715
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Chloride; Week 24; n=123	1.32 Millimoles per liter Standard Deviation 4.758
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Glucose; Week 4; n=130	-0.343 Millimoles per liter Standard Deviation 1.7140
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Glucose; Week 8; n=126	-0.222 Millimoles per liter Standard Deviation 1.7264
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Glucose; Week12; n=126	-0.263 Millimoles per liter Standard Deviation 1.7351
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Glucose; Week 16; n=126	-0.218 Millimoles per liter Standard Deviation 1.9083
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Glucose; Week 20; n=124	-0.133 Millimoles per liter Standard Deviation 1.5598
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Glucose; Week 24; n=121	-0.246 Millimoles per liter Standard Deviation 1.4132
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Potassium; Week 4; n=132	-0.208 Millimoles per liter Standard Deviation 0.4190
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Potassium; Week 8; n=127	-0.169 Millimoles per liter Standard Deviation 0.4690
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Potassium; Week12; n=127	-0.188 Millimoles per liter Standard Deviation 0.4834
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Potassium; Week 16; n=126	-0.223 Millimoles per liter Standard Deviation 0.5053
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Potassium; Week 20; n=124	-0.147 Millimoles per liter Standard Deviation 0.5728
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Potassium; Week 24; n=123	-0.168 Millimoles per liter Standard Deviation 0.4538
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Magnesium; Week 4; n=124	0.007 Millimoles per liter Standard Deviation 0.0860
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Magnesium; Week 8; n=121	0.008 Millimoles per liter Standard Deviation 0.0900
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Magnesium; Week12; n=119	0.008 Millimoles per liter Standard Deviation 0.1032
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Magnesium; Week 16; n=118	0.002 Millimoles per liter Standard Deviation 0.0986
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Magnesium; Week 20; n=116	-0.005 Millimoles per liter Standard Deviation 0.0988
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Magnesium; Week 24; n=113	0.007 Millimoles per liter Standard Deviation 0.0990
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Sodium; Week 4; n=132	0.43 Millimoles per liter Standard Deviation 3.196
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Sodium; Week 8; n=127	0.53 Millimoles per liter Standard Deviation 3.270
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Sodium; Week12; n=127	1.01 Millimoles per liter Standard Deviation 3.048
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Sodium; Week 16; n=126	0.54 Millimoles per liter Standard Deviation 3.361
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Sodium; Week 20; n=124	0.84 Millimoles per liter Standard Deviation 3.050
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Sodium; Week 24; n=123	0.58 Millimoles per liter Standard Deviation 4.485
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Inorganic Phosphorus; Week 4; n=129	-0.064 Millimoles per liter Standard Deviation 0.2729
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Inorganic Phosphorus; Week 8; n=124	-0.085 Millimoles per liter Standard Deviation 0.3164
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Inorganic Phosphorus; Week12; n=124	-0.058 Millimoles per liter Standard Deviation 0.4237
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Inorganic Phosphorus; Week 16; n=123	-0.075 Millimoles per liter Standard Deviation 0.3298
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Inorganic Phosphorus; Week 20; n=121	-0.091 Millimoles per liter Standard Deviation 0.2792
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Inorganic Phosphorus; Week 24; n=120	-0.037 Millimoles per liter Standard Deviation 0.5258
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Triglycerides; Week 4; n=131	-0.116 Millimoles per liter Standard Deviation 0.6109
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Triglycerides; Week 8; n=127	-0.079 Millimoles per liter Standard Deviation 0.5917
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Triglycerides; Week12; n=126	-0.119 Millimoles per liter Standard Deviation 0.7142
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Triglycerides; Week 16; n=126	-0.124 Millimoles per liter Standard Deviation 0.8533
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Triglycerides; Week 20; n=124	-0.211 Millimoles per liter Standard Deviation 0.6071
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Triglycerides; Week 24; n=122	-0.222 Millimoles per liter Standard Deviation 0.6796
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Urea/BUN; Week 4; n=133	-0.438 Millimoles per liter Standard Deviation 1.5434
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Urea/BUN; Week 8; n=127	-0.527 Millimoles per liter Standard Deviation 1.9777
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Urea/BUN; Week12; n=127	-0.542 Millimoles per liter Standard Deviation 1.8160
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Urea/BUN; Week 16; n=126	-0.655 Millimoles per liter Standard Deviation 1.8838
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Urea/BUN; Week 20; n=125	-0.821 Millimoles per liter Standard Deviation 1.8408
Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 Urea/BUN; Week 24; n=123	-0.635 Millimoles per liter Standard Deviation 1.9606

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population.

Urine samples were collected for urinalysis at Baseline and Week 24. The Number of participants with urinalysis to negative and positives (trace, +, ++ and +++) data at Baseline and Week 24 are summarized for urine bilirubin (UBIL), urine glucose (UGLU), urine ketones (UKET), urine nitrite (UNIT), urine protein (UM) and urine urobilinogen (UUBIL) were performed with dipstick method. Other urinalysis parameters included urine pH (UpH), urine specific gravity (USG). The Baseline value is defined as the last pre-treatment value observed.

Outcome measures

Measure	Ambrisentan n=134 Participants Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Number of Participants With Urinalysis Data at Baseline and Week 24 UBIL; Baseline; negative	125 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UBIL; Baseline; positive	7 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UBIL; Week24; negative	102 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UBIL; Week 24; positive	8 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UGLU; Baseline; negative	132 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UGLU; Baseline; positive	0 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UGLU; Week24; negative	109 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UGLU; Week 24; positive	1 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UKET; Baseline; negative	126 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UKET; Baseline; positive	6 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UKET; Week24; negative	101 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UKET; Week 24; positive	9 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UNIT; Baseline; negative	129 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UNIT; Baseline; positive	3 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UNIT; Week24; negative	108 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UNIT; Week 24; positive	2 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UM; Baseline; negative	87 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UM; Baseline; positive	45 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UM; Week24; negative	73 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UM; Week 24; positive	37 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UUBIL; Baseline; negative	109 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UUBIL; Baseline; positive	23 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UUBIL; Week24; negative	95 Participants
Number of Participants With Urinalysis Data at Baseline and Week 24 UUBIL; Week 24; positive	15 Participants

Adverse Events

Ambrisentan

Serious events: 11 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ambrisentan n=134 participants at risk Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
Cardiac disorders Atrial flutter	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Cardiac disorders Cardiac failure	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Cardiac disorders Supraventricular tachycardia	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
General disorders Sudden cardiac death	1.5% 2/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
General disorders Oedema peripheral	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Infections and infestations Bronchitis	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Infections and infestations Lung infection	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Infections and infestations Pneumonia	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Gastrointestinal disorders Ascites	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Nervous system disorders Cerebral haemorrhage	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Renal and urinary disorders Cystitis glandularis	0.75% 1/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.

Other adverse events

Measure	Ambrisentan n=134 participants at risk Participants received one tablet of 5 milligrams (mg) ambrisentan (AMB) once daily (QD) for the first 12 Weeks. After 12 Weeks, the AMB dose was titrated to either one tablet of 5 mg QD or one tablet of 10 mg QD, as determined by the investigator for another 12 Weeks.
General disorders Oedema peripheral	11.2% 15/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Vascular disorders Flushing	8.2% 11/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Investigations Alanine aminotransferase increased	6.7% 9/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Investigations Aspartate aminotransferase increased	6.7% 9/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Investigations Blood bilirubin increased	6.7% 9/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Investigations Gamma-glutamyltransferase increased	5.2% 7/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Nervous system disorders Headache	5.2% 7/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Gastrointestinal disorders Nausea	5.2% 7/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	4.5% 6/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Metabolism and nutrition disorders Decreased appetite	4.5% 6/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Nervous system disorders Dizziness	4.5% 6/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	4.5% 6/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.
Investigations Blood glucose increased	3.7% 5/134 • On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug (up to Week 24) SAEs and non-serious AEs were reported for members of the safety population, comprised of all participants who had received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER