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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01808313

Collaborator

(none)

134

Enrollment

Locations

Arm

20.4

Actual Duration (Months)

11.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open label, single-arm, non-controlled, multicentre study will determine the effect of ambrisentan on exercise capacity (6MWT) in Chinese subjects with PAH. The study consists of a screening period of 4 weeks, a 12-week primary evaluation period (PEP) and a 12-week dose-adjustment period (DAP). Ambrisentan 5 mg will be administered to eligible subjects for 12 weeks (PEP).

Condition or Disease	Intervention/Treatment	Phase
Vascular Disease	Drug: ambrisentan	Phase 3

Detailed Description

Pulmonary arterial hypertension (PAH) consists of a group of progressive and incurable diseases of the pulmonary vasculature. These are characterised by profound vasoconstriction and abnormal proliferation of smooth muscle cells in the walls of the pulmonary arteries, which leads to a progressive increase in pulmonary vascular resistance (PVR) and sustained elevations in pulmonary artery pressure (PAP). A variety of drug classes have been used to treat PAH but no single compound has yet been shown to be effective in treating all patients with the disease. Three widely used treatment options are calcium channel blockers (CCBs), diuretics and anticoagulants but all have varying responses.There is a lack of clinical data on ambrisentan among the Chinese population,Ambrisentan is conditionally approved for the treatment of PAH in China.A clinical trial with a minimum of 100 patients in the ambrisentan arm was requested by SFDA.Several PAH medications have been approved in China, so a placebo-controlled study is not ethically appropriate while an active control non-inferiority design is unfeasible due to sample size requirements and inconsistency in indications.

Study Design

Study Type:

Interventional

Actual Enrollment :

134 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label Phase IIIb Study to Evaluate Efficacy and Safety of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)

Actual Study Start Date :

Dec 1, 2012

Actual Primary Completion Date :

Aug 15, 2014

Actual Study Completion Date :

Aug 15, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ambrisentan ambrisentan 5 mg will be administered to eligible subjects for 12 weeks	Drug: ambrisentan Ambrisentan 5 mg will be administered to eligible subjects for 12 weeks

Arm

Intervention/Treatment

Experimental: ambrisentan

ambrisentan 5 mg will be administered to eligible subjects for 12 weeks

Drug: ambrisentan

Ambrisentan 5 mg will be administered to eligible subjects for 12 weeks

Outcome Measures

Primary Outcome Measures

Change From Baseline in 6-minutes Walk Test (6MWT) at Week 12 [Baseline and Week 12]
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.

Secondary Outcome Measures

Change From Baseline in 6MWT at Week 24 [Baseline and Week 24]
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.
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 [Baseline, Week 12 and Week 24]
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.
Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 [Baseline, Week 12 and Week 24]
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.
Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Weeks 12 and 24 [Baseline, Week 12 and Week 24]
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.
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 [Baseline up to Week 24]
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.
Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation [From the start of study treatment up to Week 24]
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.
Number of Participants With Physical Examination Findings [Baseline, Week 12 and Week 24]
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.
Change From Baseline in Electrocardiogram (ECG) Heart Rate Values at Weeks 12 and 24 [Baseline, Week 12 and Week 24]
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.
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 [Baseline, Week 12 and Week 24]
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.
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
Oral Temperature [Baseline]
Oral temperature was used to monitor vital signs and collected at the Screening visit.
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 [Baseline up to Week 24]
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.
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 [Baseline up to Week 24]
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.
Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
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 [Baseline up to Week 24]
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.
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 [Baseline up to Week 24]
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.
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 [Baseline up to Week 24]
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.
Number of Participants With Urinalysis Data at Baseline and Week 24 [Baseline and Week 24]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed written informed consent prior to beginning study-related procedures.
Subject must be between 18-75 years of age, inclusive, at the Screening Visit.
Subjects must weight ≥40 kg at the Screening Visit.
Subjects must have symptomatic or severe PAH (WHO functional class II or III) and be categorised as class 1 PAH (defined by the Updated Clinical Classification of Pulmonary Hypertension 2009), due to iPAH, congenital heart disease-congenital heart defects repaired greater than 1 year prior to screening (i.e., atrial septal defects, ventricular septal defects or patent ductus arteriosus) or CTD-related PAH (e.g., limited scleroderma, diffuse scleroderma, mixed CTD, systemic lupus erythematosus or overlap syndrome).

NOTE: subjects with portopulmonary hypertension and pulmonary venoocclusive disease are NOT eligible for the study.

Subjects must have had a right heart catheterisation within 6 months prior to screening and meet all of the following haemodynamic criteria:

Mean PAP ≥ 25 mmHg.
A PVR ≥ 240 dyn/sec/cm5.
A PCWP or left ventricular (LV) end-diastolic pressure of ≤ 15 mmHg.

Subjects must be able to walk a distance of at least 150 m but no more than 450 m. In addition, the screening and baseline 6MWT test values must not vary by greater than 10% (calculated using (baseline - screening)/screening with the result to be between -0.1 and 0.1).
Subjects must meet both of the following pulmonary function criteria. The tests should have been completed no more than 24 weeks prior to the Screening Visit, if not performed within the previous 24 weeks, the test must be completed at Day 0:

Total lung capacity (TLC) ≥ 60% of predicted normal.
Forced expiratory volume in one second (FEV1) ≥ 55% of predicted normal.

Subjects receiving CCBs must be on stable therapy (i.e., the dose level does not need to change to maintain disease control) for at least 1 month prior to the Screening Visit.
Subjects receiving 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) must be on stable therapy (i.e., the dose level does not need to change to maintain disease control) for at least 12 weeks prior to the Screening Visit.
Female subjects of childbearing potential must have a negative pregnancy test at the Screening Visit and Day 0.
Female subjects of childbearing potential who are sexually active must agree to use two reliable methods of contraception (as described in Appendix 3 ) from the Screening Visit until study completion and for at least 30 days following the last dose of IP. Subjects who have had a Copper T 380A intrauterine device (IUD) or LNg 20 IUD inserted are not required to use an additional method of contraception.
Subject must agree not to participate in a clinical study involving another IP or device throughout this study.

Exclusion Criteria:

The subject has received PAH therapy (PDE-5 inhibitors, ERA, chronic prostanoid*) within 4 weeks prior to the Screening Visit.

*Prostanoid use is classed as chronic when treatment continues for more than 7 days.

The subject has received intravenous inotropes (e.g., dopamine, dobutamine) within 2 weeks prior to the Screening Visit.
The subject has previously been discontinued from ERA treatment (e.g., bosentan) due to safety or tolerance issues other than those associated with liver function abnormalities.
The subject has a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is >2 x the upper limit of normal (ULN) at the Screening Visit.
The subject has serum bilirubin value that is >1.5 x ULN at the Screening Visit.
The subject has severe hepatic impairment (Child-Pugh class C with or without cirrhosis) at the Screening Visit.
The subject has severe renal impairment (creatinine clearance <30 mL/min) at the Screening Visit.
The subject has clinically significant anaemia, defined as haemoglobin concentration <10 g/dL or haematocrit <30% at the Screening Visit.
The subject has a laboratory result, physical examination finding, medical history incident or other finding, which is a contraindication for treatment with an ERA. Contraindications for treatment include, but are not limited to, evidence of elevated liver functions test or previously experiencing an event that would be defined as a serious AE (SAE) in a clinical trial (see Section 6.3.3.2), which was attributed to treatment with an ERA.
The subject has severe hypotension (either diastolic blood pressure <50 mmHg or systolic blood pressure <90 mmHg).
The subject has, in the opinion of the Investigator, clinically significant aortic or mitral valve disease, pericardial constriction, restrictive or congestive cardiomyopathy, life-threatening cardiac arrhythmias, significant LV dysfunction (defined as LV ejection fraction <45%), LV outflow obstruction, symptomatic coronary artery disease, autonomic hypotension or fluid depletion.
The subject has a history of malignancies within the past 5 years, with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix.
The subject has cardiovascular, liver, renal, haematological, gastrointestinal, immunological, endocrine, metabolic or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject.
A female subject who is pregnant or breastfeeding.
The subject has demonstrated non-compliance with previous medical regimens or is unable to comply with the procedures described in this protocol.
The subject has a history of abusing alcohol or drugs of abuse (including amphetamines, methamphetamines, opiates, cannabinoids, cocaine, benzodiazepines or barbiturates) within 12 months prior to the Screening Visit. Use of such drugs if prescribed by a Doctor and used according to the prescription would not exclude a subject.
The subject has participated in a clinical study involving another IP or device within 4 weeks or five half-lives of an IP, whichever is longer, before the Screening Visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Harbin	Heilongjiang	China	150001
2	GSK Investigational Site	Wuhan	Hubei	China	430022
3	GSK Investigational Site	Hunan	Hunan	China	410008
4	GSK Investigational Site	Changchun	Jilin	China	130021
5	GSK Investigational Site	Xian	Shaanxi	China	710032
6	GSK Investigational Site	Jinan	Shandong	China	250012
7	GSK Investigational Site	Beijing		China	100032
8	GSK Investigational Site	Beijing		China	100034
9	GSK Investigational Site	Beijing		China	100037
10	GSK Investigational Site	Beijing		China	100038
11	GSK Investigational Site	Shanghai		China	200001
12	GSK Investigational Site	Shanghai		China	200433

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT01808313

Other Study ID Numbers:

115812

First Posted:

Mar 11, 2013

Last Update Posted:

Jun 6, 2017

Last Verified:

May 1, 2017

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension

Hypertension

Vascular Diseases

Ambrisentan

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	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).

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Period Title: Overall Study
STARTED	133
COMPLETED	123
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Ambrisentan
Arm/Group Description	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 Participants	133
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.1 (10.25)
Sex: Female, Male (Count of Participants)
Female	113 85%
Male	20 15%
Race/Ethnicity, Customized (Particiopants) [Number]
Asian-East Asian Heritage	133

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in 6-minutes Walk Test (6MWT) at Week 12
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
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

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	133
Mean (Standard Deviation) [Meters]	53.59 (64.494)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	53.59
	Confidence Interval	(2-Sided) 95% 42.53 to 64.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in 6MWT at Week 24
Description	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.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	133
Mean (Standard Deviation) [Meters]	64.36 (91.173)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	64.36
	Confidence Interval	(2-Sided) 95% 48.72 to 80.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24
Description	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.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	133
Improved by 2 classes at Week 12	0 0%
Improved by 1 class at Week 12	44 33.1%
Not changing at Week 12	84 63.2%
Worsened by 1 class at Week 12	4 3%
Worsened by 2 classes at Week 12	1 0.8%
Improved by 2 classes at Week 24	0 0%
Improved by 1 class at Week 24	51 38.3%
Not changing at Week 24	77 57.9%
Worsened by 1 class at Week 24	3 2.3%
Worsened by 2 classes at Week 24	2 1.5%

4. Secondary Outcome

Title	Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24
Description	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.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	133
Week 12	-0.34 (1.521)
Week 24	-0.22 (1.952)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon signed-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon signed-rank test
	Comments

5. Secondary Outcome

Title	Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Weeks 12 and 24
Description	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.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	133
Week 12, n=123	0.44 (2.687)
Week 24, n=122	0.37 (3.103)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon signed-rank test
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95% 0.366 to 0.519
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 12

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon signed-rank test
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95% 0.303 to 0.453
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24

6. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

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

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Death at Week 12	2 1.5%
Lung Transplant at Week 12	0 0%
Hospitalization for PAH at Week 12	0 0%
Atrial Septostomy at Week 12	0 0%
IP discon (additional medication) at Week 12	0 0%
Death at Week 24	3 2.3%
Lung Transplant at Week 24	0 0%
Hospitalization for PAH at Week 24	1 0.8%
Atrial Septostomy at Week 24	0 0%
IP discon (additional medication) at Week 24	0 0%

7. Secondary Outcome

Title	Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation
Description	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.
Time Frame	From the start of study treatment up to Week 24

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Any AEs	91 68.4%
Any SAEs	11 8.3%
AEs leading to discontinuation	4 3%

8. Secondary Outcome

Title	Number of Participants With Physical Examination Findings
Description	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.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Number [Participants]	NA NaN

9. Secondary Outcome

Title	Change From Baseline in Electrocardiogram (ECG) Heart Rate Values at Weeks 12 and 24
Description	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.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	128
Week 12, n=124	-2.0 (16.65)
Week 24, n=118	-4.6 (14.68)

10. Secondary Outcome

Title	Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24
Description	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.
Time Frame	Baseline, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
PR interval, Week 12, n=122	0.7 (16.55)
PR interval, Week 24, n=117	1.5 (14.84)
QRS duration, Week 12, n=124	-1.5 (15.84)
QRS duration, Week 24, n=118	0.7 (14.40)
Uncorrected QT Interval, Week 12, n=124	-0.7 (37.44)
Uncorrected QT Interval, Week 24, n=118	6.8 (40.41)
Corrected QTcB interval, Week 12, n=123	-4.9 (29.74)
Corrected QTcB interval, Week 24, n=117	-1.5 (37.25)

11. Secondary Outcome

Title	Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	133
SBP; pre-6MWT; Week 4; n=131	-1.6 (11.57)
SBP; post-6MWT; Week 4; n=131	0.7 (15.36)
SBP; pre-6MWT; Week 8; n=126	-2.2 (13.89)
SBP; post-6MWT, Week 8; n=126	2.3 (17.36)
SBP; pre-6MWT; Week 12; n=126	-1.9 (15.08)
SBP; post-6MWT; Week 12; n=125	0.3 (18.23)
SBP; pre-6MWT; Week 16; n=124	-1.8 (14.55)
SBP; post-6MWT; Week 16; n=123	1.7 (17.71)
SBP; pre-6MWT; Week 20; n=122	-3.3 (14.42)
SBP; post-6MWT, Week 20; n=122	1.3 (18.07)
SBP; pre-6MWT; Week 24; n=123	-3.4 (15.14)
SBP; post-6MWT; Week 24; n=123	1.0 (19.01)
DBP; pre-6MWT; Week 4; n=131	-3.2 (9.30)
DBP; post-6MWT; Week 4; n=131	-1.6 (11.19)
DBP; pre-6MWT; Week 8; n=126	-3.6 (9.73)
DBP; post-6MWT; Week 8; n=126	-1.8 (11.48)
DBP; pre-6MWT; Week 12; n=126	-3.5 (10.39)
DBP; post-6MWT; Week 12; n=125	-4.2 (12.84)
DBP; pre-6MWT; Week 16; n=124	-5.0 (11.66)
DBP; post-6MWT; Week 16; n=123	-3.0 (14.20)
DBP; pre-6MWT; Week 20; n=122	-4.6 (10.97)
DBP; post-6MWT; Week 20; n=122	-2.5 (14.37)
DBP; pre-6MWT; Week 24; n=123	-4.6 (12.35)
DBP; post-6MWT; Week 24; n=123	-2.5 (13.30)

12. Secondary Outcome

Title	Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	133
Heart Rate; pre-6MWT; Week 4; n=131	-0.7 (12.12)
Heart Rate; post-6MWT; Week 4; n=131	-2.1 (18.26)
Heart Rate; pre-6MWT; Week 8; n=126	-1.2 (13.10)
Heart Rate; post-6MWT, Week 8; n=126	-0.2 (17.39)
Heart Rate; pre-6MWT; Week 12; n=126	-1.7 (12.27)
Heart Rate; post-6MWT; Week 12; n=124	0.6 (18.23)
Heart Rate; post-6MWT 1M; Week 12; n=124	-0.9 (15.11)
Heart Rate; post-6MWT 2 M; Week 12; n=124	-2.2 (13.51)
Heart Rate; post-6MWT 3 M; Week 12; n=125	-1.2 (13.90)
Heart Rate; Recovery to Pre-6MWT; Week 12; n=125	-1.5 (12.50)
Heart Rate; pre-6MWT; Week 16; n=124	-2.6 (13.10)
Heart Rate; post-6MWT; Week 16; n=123	0.5 (19.81)
Heart Rate; pre-6MWT; Week 20; n=122	-3.6 (12.45)
Heart Rate; post-6MWT, Week 20; n=122	0.4 (20.82)
Heart Rate; pre-6MWT; Week 24; n=123	-0.8 (13.34)
Heart Rate; post-6MWT; Week 24; n=123	3.4 (21.88)
Heart Rate; post-6MWT 1 M; Week 24; n=121	0.3 (16.57)
Heart Rate; post-6MWT 2 M; Week 24; n=121	-0.5 (13.95)
Heart Rate; post-6MWT 3 M; Week 24; n=122	-0.2 (13.41)
Heart Rate; Recovery to Pre-6MWT; Week 24; n=123	-0.4 (13.39)

13. Secondary Outcome

Title	Oral Temperature
Description	Oral temperature was used to monitor vital signs and collected at the Screening visit.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Mean (Full Range) [Celsius]	36.4

14. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
ALT; BL <=1 x ULN shift to >3 x ULN post-BL;n=133	0 0%
ALT; >1 x - <3 x ULN shift to >3 x ULN; n=133	3 2.3%
ALP; <=1 x ULN shift to >3 x ULN; n=132	0 0%
ALP; >1 x - <3 x ULN shift to >3 x ULN; n=132	0 0%
AST; <=1 x ULN shift to >3 x ULN; n=133	0 0%
AST; >1 x - <3 x ULN shift to >3 x ULN; n=133	2 1.5%
BILT; >1 x - <2 x ULN shift to >2 x ULN; n=133	1 0.8%
BILT; >1 x - <3 x ULN shift to >2 x ULN; n=133	3 2.3%
BILT; >1 x - >2 x ULN shift to >2 x ULN; n=133	1 0.8%

15. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Basophils; Week 4; n=133	-0.010 (0.0434)
Basophils; Week 8; n=125	-0.007 (0.0479)
Basophils; Week12; n=125	-0.009 (0.0438)
Basophils; Week 16; n=125	-0.006 (0.0484)
Basophils; Week 20; n=125	-0.002 (0.0366)
Basophils; Week 24; n=123	-0.002 (0.0792)
Eosinophils; Week 4; n=133	-0.0077 (0.0515)
Eosinophils; Week 8; n=125	-0.0004 (0.0588)
Eosinophils; Week 12; n=125	0.0012 (0.0603)
Eosinophils; Week 16; n=125	0.0126 (0.1466)
Eosinophils; Week 20; n=125	0.0014 (0.0582)
Eosinophils; Week 24; n=123	0.0014 (0.0854)
Lymphocytes; Week 4; n=133	-0.257 (0.5558)
Lymphocytes; Week 8; n=125	-0.201 (0.6116)
Lymphocytes; Week 12; n=125	-0.284 (0.5743)
Lymphocytes; Week 16; n=125	-0.295 (0.5821)
Lymphocytes; Week 20; n=125	-0.378 (0.6600)
Lymphocytes; Week 24; n=123	-0.363 (0.6897)
Monocytes; Week 4; n=133	-0.011 (0.1684)
Monocytes; Week 8; n=125	-0.013 (0.1713)
Monocytes; Week 12; n=125	-0.032 (0.1659)
Monocytes; Week 16; n=125	-0.019 (0.1665)
Monocytes; Week 20; n=125	-0.044 (0.1574)
Monocytes; Week 24; n=123	-0.000 (0.4885)
Total Neutrophils; Week 4; n=133	-0.4093 (1.7597)
Total Neutrophils; Week 8; n=125	-0.4209 (1.8660)
Total Neutrophils; Week 12; n=125	-0.5958 (1.8947)
Total Neutrophils; Week 16; n=125	-0.7201 (2.1282)
Total Neutrophils; Week 20; n=125	-0.9510 (2.0706)
Total Neutrophils; Week 24; n=123	-0.9247 (2.2646)
Platelet Count; Week 4; n=133	-4.80 (41.562)
Platelet Count; Week 8; n=125	-3.00 (49.357)
Platelet Count; Week 12; n=125	-1.56 (54.690)
Platelet Count; Week 16; n=125	-6.04 (50.227)
Platelet Count; Week 20; n=125	-7.89 (52.007)
Platelet Count; Week 24; n=123	-4.75 (45.181)
WBC Count; Week 4; n=133	-0.689 (1.9433)
WBC count; Week 8; n=125	-0.642 (2.1480)
WBC count; Week 12; n=125	-0.925 (2.1708)
WBC Count; Week 16; n=125	-1.050 (2.3951)
WBC count; Week 20; n=125	-1.387 (2.2706)
WBC count; Week 24; n=123	-1.342 (2.5167)

16. Secondary Outcome

Title	Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Hemoglobin; Week 4; n=133	-7.46 (11.345)
Hemoglobin; Week 8; n=125	-6.80 (13.642)
Hemoglobin; Week12; n=125	-6.29 (14.269)
Hemoglobin; Week 16; n=125	-6.87 (14.245)
Hemoglobin; Week 20; n=125	-8.19 (14.862)
Hemoglobin; Week 24; n=123	-6.56 (14.724)

17. Secondary Outcome

Title	Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Hematocrit; Week 4; n=133	-0.0168 (0.0587)
Hematocrit; Week 8; n=125	-0.0209 (0.0412)
Hematocrit; Week12; n=125	-0.0180 (0.0420)
Hematocrit; Week 16; n=125	-0.0179 (0.0443)
Hematocrit; Week 20; n=125	-0.0220 (0.0459)
Hematocrit; Week 24; n=123	-0.0176 (0.0422)

18. Secondary Outcome

Title	Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Mean Corpuscle Hemoglobin; Week 4; n=133	0.258 (1.4064)
Mean Corpuscle Hemoglobin; Week 8; n=125	0.405 (1.5405)
Mean Corpuscle Hemoglobin; Week12; n=125	0.347 (2.1082)
Mean Corpuscle Hemoglobin; Week 16; n=125	0.185 (2.0053)
Mean Corpuscle Hemoglobin; Week 20; n=125	0.019 (2.0040)
Mean Corpuscle Hemoglobin; Week 24; n=123	-0.035 (2.0831)

19. Secondary Outcome

Title	Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Mean corpuscle volume; Week 4; n=133	0.906 (2.8849)
Mean corpuscle volume; Week 8; n=125	1.362 (3.8958)
Mean corpuscle volume; Week12; n=125	0.485 (7.4220)
Mean corpuscle volume; Week 16; n=125	0.725 (6.6333)
Mean corpuscle volume; Week 20; n=125	0.587 (4.7209)
Mean corpuscle volume; Week 24; n=123	0.392 (4.8609)

20. Secondary Outcome

Title	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
RBC count; Week 4; n=133	-0.2773 (0.3678)
RBC count; Week 8; n=125	-0.2987 (0.4781)
RBC count; Week12; n=125	-0.2520 (0.4672)
RBC count; Week 16; n=125	-0.2595 (0.5066)
RBC count; Week 20; n=125	-0.2733 (0.5414)
RBC count; Week 24; n=123	-0.2182 (0.4802)

21. Secondary Outcome

Title	Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Albumin; Week 4; n=132	1.01 (4.274)
Albumin; Week 8; n=126	1.09 (3.717)
Albumin; Week12; n=126	1.09 (4.105)
Albumin; Week 16; n=126	1.05 (4.098)
Albumin; Week 20; n=121	0.64 (4.625)
Albumin; Week 24; n=120	1.31 (4.390)
Globulin; Week 4; n=112	-1.63 (5.083)
Globulin; Week 8; n=106	-2.17 (6.083)
Globulin; Week12; n=107	-2.38 (6.456)
Globulin; Week 16; n=107	-2.24 (6.120)
Globulin; Week 20; n=103	-2.57 (6.126)
Globulin; Week 24; n=103	-2.25 (6.251)
Total Protein; Week 4; n=132	-1.19 (9.058)
Total Protein; Week 8; n=127	-1.25 (8.555)
Total Protein; Week12; n=126	-1.57 (8.835)
Total Protein; Week 16; n=126	-1.37 (7.854)
Total Protein; Week 20; n=122	-2.60 (10.129)
Total Protein; Week 24; n=121	-0.91 (8.841)

22. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
ALP; Week 4; n=131	-4.20 (14.945)
ALP; Week 8; n=124	-6.19 (16.612)
ALP; Week12; n=125	-6.79 (16.815)
ALP; Week 16; n=122	-4.47 (18.916)
ALP; Week 20; n=124	-5.99 (18.255)
ALP; Week 24; n=121	-2.95 (23.104)
ALT; Week 4; n=133	0.07 (20.479)
ALT; Week 8; n=127	-1.58 (20.411)
ALT; Week12; n=127	-5.69 (16.770)
ALT; Week 16; n=126	-5.33 (16.064)
ALT; Week 20; n=125	-5.44 (19.143)
ALT; Week 24; n=123	-5.62 (15.734)
AST; Week 4; n=132	0.18 (24.671)
AST; Week 8; n=127	-1.55 (13.848)
AST; Week12; n=127	-3.51 (13.835)
AST; Week 16; n=125	-4.03 (12.710)
AST; Week 20; n=125	-3.80 (15.021)
AST; Week 24; n=123	-3.63 (12.091)
CK; Week 4; n=129	-1.78 (35.099)
CK; Week 8; n=123	11.21 (182.414)
CK; Week12; n=124	1.62 (105.342)
CK; Week 16; n=121	0.07 (100.783)
CK; Week 20; n=120	-1.79 (86.528)
CK; Week 24; n=116	0.32 (89.377)
GGT; Week 4; n=131	-4.67 (46.013)
GGT; Week 8; n=127	-10.91 (49.174)
GGT; Week12; n=127	-15.82 (52.509)
GGT; Week 16; n=124	-13.98 (55.130)
GGT; Week 20; n=125	-20.42 (58.287)
GGT; Week 24; n=122	-21.84 (56.557)
LDH; Week 4; n=122	-20.45 (53.720)
LDH; Week 8; n=118	-19.24 (80.068)
LDH; Week12; n=118	-28.15 (77.867)
LDH; Week 16; n=117	-29.37 (82.565)
LDH; Week 20; n=117	-26.65 (81.007)
LDH; Week 24; n=113	-27.38 (74.551)

23. Secondary Outcome

Title	Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Direct Bilirubin; Week 4; n=131	-0.326 (2.0821)
Direct Bilirubin; Week 8; n=126	-0.538 (2.5429)
Direct Bilirubin; Week12; n=127	-0.787 (2.5038)
Direct Bilirubin; Week 16; n=126	-0.778 (2.7692)
Direct Bilirubin; Week 20; n=125	-0.780 (2.5072)
Direct Bilirubin; Week 24; n=122	-0.752 (2.7299)
Total Bilirubin; Week 4; n=131	-0.72 (5.903)
Total Bilirubin; Week 8; n=127	-1.12 (6.089)
Total Bilirubin; Week12; n=127	-0.49 (17.178)
Total Bilirubin; Week 16; n=126	-1.49 (6.866)
Total Bilirubin; Week 20; n=125	-1.65 (6.329)
Total Bilirubin; Week 24; n=123	-1.25 (6.927)
Creatinine; Week 4; n=133	-1.924 (10.1256)
Creatinine; Week 8; n=127	-1.968 (10.7823)
Creatinine; Week12; n=127	-0.759 (9.2949)
Creatinine; Week 16; n=126	-0.847 (10.0814)
Creatinine; Week 20; n=125	-0.970 (9.3502)
Creatinine; Week 24; n=123	-0.217 (9.9447)
Uric Acid; Week 4; n=129	-13.289 (82.7246)
Uric Acid; Week 8; n=125	-13.159 (87.0456)
Uric Acid; Week12; n=125	-16.580 (83.7145)
Uric Acid; Week 16; n=124	-16.149 (87.9857)
Uric Acid; Week 20; n=119	-24.584 (94.9378)
Uric Acid; Week 24; n=121	-13.168 (95.0694)

24. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
Calcium; Week 4; n=132	-0.009 (0.1321)
Calcium; Week 8; n=127	-0.020 (0.1386)
Calcium; Week12; n=127	-0.008 (0.1340)
Calcium; Week 16; n=126	-0.015 (0.1470)
Calcium; Week 20; n=124	-0.006 (0.1513)
Calcium; Week 24; n=123	0.007 (0.1440)
Cholesterol; Week 4; n=132	-0.034 (0.7416)
Cholesterol; Week 8; n=126	-0.062 (0.8776)
Cholesterol; Week12; n=126	-0.180 (0.9450)
Cholesterol; Week 16; n=126	-0.281 (0.8570)
Cholesterol; Week 20; n=125	-0.277 (0.8482)
Cholesterol; Week 24; n=121	-0.253 (0.8340)
Chloride; Week 4; n=131	0.48 (7.594)
Chloride; Week 8; n=127	1.02 (3.858)
Chloride; Week12; n=127	1.51 (3.409)
Chloride; Week 16; n=126	1.01 (3.995)
Chloride; Week 20; n=124	1.40 (3.715)
Chloride; Week 24; n=123	1.32 (4.758)
Glucose; Week 4; n=130	-0.343 (1.7140)
Glucose; Week 8; n=126	-0.222 (1.7264)
Glucose; Week12; n=126	-0.263 (1.7351)
Glucose; Week 16; n=126	-0.218 (1.9083)
Glucose; Week 20; n=124	-0.133 (1.5598)
Glucose; Week 24; n=121	-0.246 (1.4132)
Potassium; Week 4; n=132	-0.208 (0.4190)
Potassium; Week 8; n=127	-0.169 (0.4690)
Potassium; Week12; n=127	-0.188 (0.4834)
Potassium; Week 16; n=126	-0.223 (0.5053)
Potassium; Week 20; n=124	-0.147 (0.5728)
Potassium; Week 24; n=123	-0.168 (0.4538)
Magnesium; Week 4; n=124	0.007 (0.0860)
Magnesium; Week 8; n=121	0.008 (0.0900)
Magnesium; Week12; n=119	0.008 (0.1032)
Magnesium; Week 16; n=118	0.002 (0.0986)
Magnesium; Week 20; n=116	-0.005 (0.0988)
Magnesium; Week 24; n=113	0.007 (0.0990)
Sodium; Week 4; n=132	0.43 (3.196)
Sodium; Week 8; n=127	0.53 (3.270)
Sodium; Week12; n=127	1.01 (3.048)
Sodium; Week 16; n=126	0.54 (3.361)
Sodium; Week 20; n=124	0.84 (3.050)
Sodium; Week 24; n=123	0.58 (4.485)
Inorganic Phosphorus; Week 4; n=129	-0.064 (0.2729)
Inorganic Phosphorus; Week 8; n=124	-0.085 (0.3164)
Inorganic Phosphorus; Week12; n=124	-0.058 (0.4237)
Inorganic Phosphorus; Week 16; n=123	-0.075 (0.3298)
Inorganic Phosphorus; Week 20; n=121	-0.091 (0.2792)
Inorganic Phosphorus; Week 24; n=120	-0.037 (0.5258)
Triglycerides; Week 4; n=131	-0.116 (0.6109)
Triglycerides; Week 8; n=127	-0.079 (0.5917)
Triglycerides; Week12; n=126	-0.119 (0.7142)
Triglycerides; Week 16; n=126	-0.124 (0.8533)
Triglycerides; Week 20; n=124	-0.211 (0.6071)
Triglycerides; Week 24; n=122	-0.222 (0.6796)
Urea/BUN; Week 4; n=133	-0.438 (1.5434)
Urea/BUN; Week 8; n=127	-0.527 (1.9777)
Urea/BUN; Week12; n=127	-0.542 (1.8160)
Urea/BUN; Week 16; n=126	-0.655 (1.8838)
Urea/BUN; Week 20; n=125	-0.821 (1.8408)
Urea/BUN; Week 24; n=123	-0.635 (1.9606)

25. Secondary Outcome

Title	Number of Participants With Urinalysis Data at Baseline and Week 24
Description	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.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
Measure Participants	134
UBIL; Baseline; negative	125 94%
UBIL; Baseline; positive	7 5.3%
UBIL; Week24; negative	102 76.7%
UBIL; Week 24; positive	8 6%
UGLU; Baseline; negative	132 99.2%
UGLU; Baseline; positive	0 0%
UGLU; Week24; negative	109 82%
UGLU; Week 24; positive	1 0.8%
UKET; Baseline; negative	126 94.7%
UKET; Baseline; positive	6 4.5%
UKET; Week24; negative	101 75.9%
UKET; Week 24; positive	9 6.8%
UNIT; Baseline; negative	129 97%
UNIT; Baseline; positive	3 2.3%
UNIT; Week24; negative	108 81.2%
UNIT; Week 24; positive	2 1.5%
UM; Baseline; negative	87 65.4%
UM; Baseline; positive	45 33.8%
UM; Week24; negative	73 54.9%
UM; Week 24; positive	37 27.8%
UUBIL; Baseline; negative	109 82%
UUBIL; Baseline; positive	23 17.3%
UUBIL; Week24; negative	95 71.4%
UUBIL; Week 24; positive	15 11.3%

Adverse Events

	Ambrisentan
Time Frame	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)
Adverse Event Reporting Description	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.

Arm/Group Title	Ambrisentan
Arm/Group Description	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.
All Cause Mortality
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	11/134 (8.2%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	1/134 (0.7%)
Cardiac disorders
Atrial flutter	1/134 (0.7%)
Cardiac failure	1/134 (0.7%)
Supraventricular tachycardia	1/134 (0.7%)
Gastrointestinal disorders
Ascites	1/134 (0.7%)
Diarrhoea	1/134 (0.7%)
General disorders
Sudden cardiac death	2/134 (1.5%)
Oedema peripheral	1/134 (0.7%)
Infections and infestations
Bronchitis	1/134 (0.7%)
Lung infection	1/134 (0.7%)
Pneumonia	1/134 (0.7%)
Nervous system disorders
Cerebral haemorrhage	1/134 (0.7%)
Renal and urinary disorders
Cystitis glandularis	1/134 (0.7%)
Other (Not Including Serious) Adverse Events
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	59/134 (44%)
Gastrointestinal disorders
Nausea	7/134 (5.2%)
General disorders
Oedema peripheral	15/134 (11.2%)
Infections and infestations
Upper respiratory tract infection	6/134 (4.5%)
Investigations
Alanine aminotransferase increased	9/134 (6.7%)
Aspartate aminotransferase increased	9/134 (6.7%)
Blood bilirubin increased	9/134 (6.7%)
Gamma-glutamyltransferase increased	7/134 (5.2%)
Blood glucose increased	5/134 (3.7%)
Metabolism and nutrition disorders
Decreased appetite	6/134 (4.5%)
Nervous system disorders
Headache	7/134 (5.2%)
Dizziness	6/134 (4.5%)
Respiratory, thoracic and mediastinal disorders
Cough	6/134 (4.5%)
Vascular disorders
Flushing	11/134 (8.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT01808313

Other Study ID Numbers:

115812

First Posted:

Mar 11, 2013

Last Update Posted:

Jun 6, 2017

Last Verified:

May 1, 2017

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

Study Details

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Outcome Measures

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Statistical Analysis 1

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Statistical Analysis 1

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Statistical Analysis 1

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Outcome Measure Data

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