Vascular Disease
Conditions
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).
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.
Interventions
DRUGambrisentan
Ambrisentan 5 mg will be administered to eligible subjects for 12 weeks
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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: 1. Mean PAP ≥ 25 mmHg. 2. A PVR ≥ 240 dyn/sec/cm5. 3. 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: 1. Total lung capacity (TLC) ≥ 60% of predicted normal. 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
China
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 133 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Met Protocol-defined Stopping Criteria | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Ambrisentan |
|---|---|
| Age, Continuous | 36.1 Years STANDARD_DEVIATION 10.25 |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 133 Particiopants |
| Sex: Female, Male Female | 113 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 134 |
| serious Total, serious adverse events | 11 / 134 |
Outcome results
Primary
Change From Baseline in 6-minutes Walk Test (6MWT) at 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.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Change From Baseline in 6-minutes Walk Test (6MWT) at Week 12 | 53.59 Meters | Standard Deviation 64.494 |
p-value: <0.00195% CI: [42.53, 64.66]t-test, 2 sided
Secondary
Change From Baseline in 6MWT at 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.
Time frame: Baseline and Week 24
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ambrisentan | Change From Baseline in 6MWT at Week 24 | 64.36 Meters | Standard Deviation 91.173 |
p-value: <0.00195% CI: [48.72, 80]t-test, 2 sided
Secondary
Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 4.39 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 6.12 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
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
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 16.77 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 12.71 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 55.13 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 53.72 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
Secondary
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
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.66 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 1.866 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 54.69 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 2.148 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
Secondary
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
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.134 |
| Ambrisentan | 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 0.147 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.144 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.945 |
| Ambrisentan | 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 0.857 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.834 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 1.714 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.419 |
| Ambrisentan | 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 0.469 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.086 |
| Ambrisentan | 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 0.09 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.099 |
| Ambrisentan | 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 |
| Ambrisentan | 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 3.27 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 3.05 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 1.816 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in Electrocardiogram (ECG) Heart Rate Values at Weeks 12 and 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in Heart Rate at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 13.1 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 13.9 |
| Ambrisentan | 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 12.5 |
| Ambrisentan | 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 13.1 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in Hematocrit at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 0.042 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in Hemoglobin at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 2.004 |
| Ambrisentan | 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
Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 7.422 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 14.4 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 9.3 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 14.2 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 13.3 |
Secondary
Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 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.
Time frame: Baseline, Week 12 and Week 24
Population: ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
Comparison: Week 12p-value: <0.001Wilcoxon signed-rank test
Comparison: Week 24p-value: 0.003Wilcoxon signed-rank test
Secondary
Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Weeks 12 and 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
p-value: <0.00195% CI: [0.366, 0.519]Wilcoxon signed-rank test
p-value: <0.00195% CI: [0.303, 0.453]Wilcoxon signed-rank test
Secondary
Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 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.
Time frame: Baseline, Week 12 and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation
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
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan | Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation | Any AEs | 91 Participants |
| Ambrisentan | Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation | Any SAEs | 11 Participants |
| Ambrisentan | Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation | AEs leading to discontinuation | 4 Participants |
Secondary
Number of Participants With Physical Examination Findings
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
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ambrisentan | Number of Participants With Physical Examination Findings | NA Participants |
Secondary
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
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
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
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
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
Population: Safety Population: This population comprised of all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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 |
| Ambrisentan | 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
Number of Participants With Urinalysis Data at 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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UNIT; Baseline; positive | 3 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UNIT; Week24; negative | 108 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UNIT; Week 24; positive | 2 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UKET; Week24; negative | 101 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UKET; Week 24; positive | 9 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UBIL; Baseline; negative | 125 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UBIL; Baseline; positive | 7 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UBIL; Week24; negative | 102 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UBIL; Week 24; positive | 8 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UGLU; Baseline; negative | 132 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UGLU; Baseline; positive | 0 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UGLU; Week24; negative | 109 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UGLU; Week 24; positive | 1 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UKET; Baseline; negative | 126 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UKET; Baseline; positive | 6 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UNIT; Baseline; negative | 129 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UM; Baseline; negative | 87 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UM; Baseline; positive | 45 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UM; Week24; negative | 73 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UM; Week 24; positive | 37 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UUBIL; Baseline; negative | 109 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UUBIL; Baseline; positive | 23 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UUBIL; Week24; negative | 95 Participants |
| Ambrisentan | Number of Participants With Urinalysis Data at Baseline and Week 24 | UUBIL; Week 24; positive | 15 Participants |
Secondary
Oral Temperature
Oral temperature was used to monitor vital signs and collected at the Screening visit.
Time frame: Baseline
Population: Safety Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ambrisentan | Oral Temperature | 36.4 Celsius |