Trial Outcomes & Findings for Relative Bioavailability Study of Marketed and Lower Dose Ambrisentan in Healthy Adult Participants (NCT NCT04095286)

This was a single center, open-label, randomized, single dose, 3-period crossover study in healthy participants that compared the pharmacokinetics (PK) of a new lower dose formulation (dispersed in water and administered intact orally) of ambrisentan (AMB) tablet with the reference marketed AMB tablet (administered orally).

A total of 29 participants were enrolled at a single center in the United Kingdom.

Relative Bioavailability Study of Marketed and Lower Dose Ambrisentan in Healthy Adult Participants

Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who provided PK parameter data.

Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.

Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.

Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.

Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.

Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment were categorized as SAE.

Vital signs were measured in semi-supine position after 5 minutes rest and included Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Heart rate (HR). Data for number of participants with Post-Baseline worst case Vital Sign results relative to PCI Criteria relative to Baseline has been presented. Participants are counted in worst case category that their value changes to low, within range or high. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in "Within Range or No Change" category. Participants are counted twice if values changed 'To Low' and 'To High', so the percentages are not added to 100%. Participants with missing baseline value are assumed as within range value. PCI ranges were: SBP \[lower: \<85, upper: \>160 millimeter of mercury (mmHg)\]; DBP (lower: \<40, upper: \>110 mmHg); HR (lower: \<45, upper: \>100 beats per minute). The value at Day 1 was considered as Baseline.

12-lead ECGs were recorded in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal clinically significant ECG findings for worst case post-Baseline has been presented. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The value at Day 1 was considered as Baseline.

Blood samples were collected to analyze hemoglobin, hematocrit, lymphocytes, total neutrophils, platelet count, and white blood cell(WBC) counts. PCI ranges were hematocrit (high: \>0.54 proportion of red blood cells in blood and low: change from Baseline \<0.075); hemoglobin(high: \>180 grams per liter\[g/L\] and low: change from Baseline \<25 g/L); lymphocytes (low: \<0.8 Giga cells per liter\[GI/L\]); platelet count (low: \<100 GI/L and high: \>550 GI/L); neutrophil count (low: \<1.5 GI/L); WBC count (low: \<3 GI/L and high: \>20 GI/L). Participants were counted in worst-case category that their value changed to low, within range or no change, or high unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in ''To within Range or No Change' category. Participants were counted twice if participant had both values that changed 'To Low' and 'To High'. Baseline is defined as Day -1.

Blood samples were collected to analyze PCI ranges for aspartate amino transferase (AST), alanine amino transferase (ALT), \& alkaline phosphatase (ALP) (high: \>=2 times (\*) upper limit of normal \[ULN\] International units per liter \[IU/L\]); bilirubin (high: \>=1.5 \* ULN micromoles per liter \[µmol/L\]); calcium (low: \<2 millimoles per liter \[mmol/L\] \& high: \>2.75 mmol/L); glucose (low: \<3 \& high: \>9 mmol/L); potassium (low: \<3 \& high: \>5.5 mmol/L); sodium (low: \<130 \& high: \>150 mmol/L) \& Blood Urea Nitrogen (BUN) (high: \>=2 \* ULN µmol/L). Participants were counted in worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants were counted twice if participant had both values that changed 'To Low' \& 'To High'.

Urine samples were collected for analysis of cellular casts, granular casts, hyaline casts and red blood cells. WBCs were counted as cells per high-power field (cells/HPF). Participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented. Baseline is defined as Day -1.