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This is a single center, open-label, randomized, single-dose, three-period cross-over study in healthy participants. The aim of this study is to provide clinically relevant information on the pharmacokinetic (PK) and safety profile of a new lower dose formulation ambrisentan (AMB) tablet, which is intended for pediatric use. The study will compare the relative bioavailability of the lower dose tablet, dispersed in water and administered orally, with the reference marketed AMB tablet in healthy adults. The total study duration for each participant is expected to be approximately 9 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AMB dispersed in water/AMB oral tablet/reference AMB | Experimental | Eligible participants will receive a single oral dose of 5 milligram (mg) AMB tablet dispersed in water during treatment period 1 followed by a single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive a single oral dose of reference 5 mg AMB tablet. There will be a washout period of 7 days between doses in each treatment period. |
|
| AMB oral tablet/reference AMB/AMB dispersed in water | Experimental | Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive single dose of 5 mg AMB tablet dispersed in water. There will be a washout period of 7 days between doses in each treatment period. |
|
| Reference AMB/AMB dispersed in water/AMB oral tablet | Experimental | Eligible participants will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period. |
|
| AMB dispersed in water/reference AMB/AMB oral tablet |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AMB new formulation (1 mg) | Drug | AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition | 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. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
| Time to Cmax (Tmax) After Administration of AMB Under Fasted Condition | Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
| Time of Last Quantifiable Concentration (Tlast) After Administration of AMB Under Fasted Condition | Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [(AUC(0-inf)] After Administration of AMB Under Fasted Condition | Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] After Administration of AMB Under Fasted Condition | Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=2%) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | Cambridgeshire | CB2 2GG | United Kingdom |
IPD for this study will be made available via the Clinical Study Data Request site.
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
A total of 29 participants were enrolled at a single center in the United Kingdom.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | AMB Dispersed in Water/AMB Oral Tablet/Reference AMB | Participants received a single oral dose of 5 milligram (mg) (administered as 5 x 1 mg tablet) AMB tablet dispersed in water during treatment period 1 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB oral tablet administered intact in treatment period 2 followed by a single oral dose of reference 5 mg (administered as 1 x 5 mg tablet) AMB tablet in treatment period 3. The treatment periods were separated by a washout period of minimum 7 days. |
| FG001 | AMB Oral Tablet/Reference AMB/AMB Dispersed in Water | Participants received a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB oral tablet administered intact during treatment period 1 followed by a single dose of reference 5 mg (administered as 1 x 5 mg tablet) AMB oral tablet in treatment period 2 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB tablet dispersed in water in treatment period 3. The treatment periods were separated by a washout period of minimum 7 days. |
| FG002 | Reference AMB/AMB Dispersed in Water/AMB Oral Tablet | Participants received a single dose of reference 5 mg (administered as 1 x 5 mg tablet) AMB oral tablet during treatment period 1 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB tablet dispersed in water in treatment period 2 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB oral tablet administered intact in treatment period 3. The treatment periods were separated by a washout period of minimum 7 days. |
| FG003 | AMB Dispersed in Water/Reference AMB/AMB Oral Tablet | Participants received a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB tablet dispersed in water during treatment period 1 followed by a single dose of reference 5 mg (administered as 1 x 5 mg tablet) AMB oral tablet in treatment period 2 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB oral tablet administered intact in treatment period 3. The treatment periods were separated by a washout period of minimum 7 days. |
| FG004 | AMB Oral Tablet/AMB Dispersed in Water/Reference AMB | Participants received a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB oral tablet administered intact during treatment period 1 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB tablet dispersed in water in treatment period 2 followed by a single dose of reference 5 mg (administered as 1 x 5 mg tablet) AMB oral tablet in treatment period 3. The treatment periods were separated by a washout period of minimum 7 days. |
| FG005 | Reference AMB/AMB Oral/AMB Dispersed in Water | Participants received a single dose of reference 5 mg (administered as 1 x 5 mg tablet) AMB oral tablet during treatment period 1 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB oral tablet administered intact in treatment period 2 followed by a single dose of 5 mg (administered as 5 x 1 mg tablet) AMB tablet dispersed in water in treatment period 3. The treatment periods were separated by a washout period of minimum 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (4 Days) + Washout (7days) |
|
| ||||||||||||||||||
| Period 2 (4 Days) + Washout (7days) |
| |||||||||||||||||||
| Period 3 (4 Days) + Follow up (14 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants received a single oral dose of AMB tablet (administered as 5 x 1 mg tablet) dispersed in water (F1) or a single dose of AMB oral tablet (administered as 5 x 1 mg tablet) administered intact (F2) or a single oral dose of reference AMB tablet (R) administered as 1 x 5 mg tablet in the following six sequences F1/F2/R, F2/R/F1, R/F1/F2, F1/R/F2, F2/F1/R and R/F2/F1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition | 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. | PK Parameter Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
|
SAEs and non-SAEs were collected from the start of study treatment until the follow up (Up to 40 days)
SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who received at least one dose of study intervention. Data has been presented treatment wise.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AMB Dispersed in Water | Participants received a single dose of 5 mg AMB tablet dispersed in water and administered orally |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ocular hyperaemia | Eye disorders | MedDRA 22.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 19, 2019 | Jul 12, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 14, 2020 | Jul 12, 2020 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
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This is a three-period crossover study
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Eligible participants will receive single dose of 5 mg AMB tablet dispersed in water during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period. |
|
| AMB oral tablet/AMB dispersed in water/reference AMB | Experimental | Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of reference 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period. |
|
| Reference AMB/AMB oral/AMB dispersed in water | Experimental | Eligible participants in this arm will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB tablet dispersed in water There will be a washout period of 7 days between doses in each treatment period. |
|
| Reference AMB (5 mg) | Drug | AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose |
|
| Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
| Apparent Terminal Phase Half-life (t1/2) After Administration of AMB Under Fasted Condition | Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
| Up to 40 days |
| Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | 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. | Baseline (Day 1) and up to 40 days |
| Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | 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. | Baseline (Day 1) and up to 40 days |
| Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to 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. | Baseline (Day -1) and up to 40 days |
| Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline | 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'. | Baseline (Day -1) and up to 40 days |
| Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | 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. | Baseline (Day -1) and up to 40 days |
| Withdrawal by Subject |
|
| Adverse Event |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| AMB Oral Tablet |
Participants received a single dose of 5 mg AMB tablet administered intact orally |
| OG002 | Reference AMB | Participants received a single dose of reference 5 mg AMB tablet administered orally |
|
|
|
| Primary | Time to Cmax (Tmax) After Administration of AMB Under Fasted Condition | 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. Only those participants with data available at the specified data points were analyzed. | Posted | Median | Full Range | Hour | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
|
|
|
| Primary | Time of Last Quantifiable Concentration (Tlast) After Administration of AMB Under Fasted Condition | 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. Only those participants with data available at the specified data points were analyzed. | Posted | Median | Full Range | Hour | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
|
|
|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [(AUC(0-inf)] After Administration of AMB Under Fasted Condition | 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. Only those participants with data available at the specified data points were analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
|
|
|
|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] After Administration of AMB Under Fasted Condition | 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. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
|
|
|
|
| Primary | Apparent Terminal Phase Half-life (t1/2) After Administration of AMB Under Fasted Condition | 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. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose |
|
|
|
| Secondary | Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=2%) | 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. | Safety Population comprises of all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the intervention actually received. Only those participants with data available at the specified data points were analysed. | Posted | Count of Participants | Participants | Up to 40 days |
|
|
|
| Secondary | Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline | 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. | Safety Population. Only those participants with data available at the specified data points were analysed. | Posted | Count of Participants | Participants | Baseline (Day 1) and up to 40 days |
|
|
|
| Secondary | Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed. | Posted | Count of Participants | Participants | Baseline (Day 1) and up to 40 days |
|
|
|
| Secondary | Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles) | Posted | Count of Participants | Participants | Baseline (Day -1) and up to 40 days |
|
|
|
| Secondary | Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline | 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'. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles) | Posted | Count of Participants | Participants | Baseline (Day -1) and up to 40 days |
|
|
|
| Secondary | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed. | Posted | Count of Participants | Participants | Baseline (Day -1) and up to 40 days |
|
|
|
| 0 |
| 27 |
| 0 |
| 27 |
| 5 |
| 27 |
| EG001 | AMB Oral Tablet | Participants received a single dose of 5 mg AMB tablet administered intact orally | 0 | 25 | 0 | 25 | 7 | 25 |
| EG002 | Reference AMB | Participants received a single dose of reference 5 mg AMB tablet administered orally | 0 | 26 | 0 | 26 | 5 | 26 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Catheter site swelling | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial
| D002318 |
| Cardiovascular Diseases |
| Ratio of adjusted geometric mean |
| 1.04 |
| 2-Sided |
| 90 |
| 1.00 |
| 1.08 |
Treatment comparison between AMB oral tablet and reference AMB tablet using ratio of adjusted geometric mean and its corresponding 90% confidence interval has been presented |
| Other |
| Ratio of adjusted geometric mean |
| 1.04 |
| 2-Sided |
| 90 |
| 1.01 |
| 1.07 |
Treatment comparison between AMB oral tablet and reference AMB tablet using ratio of adjusted geometric mean and its corresponding 90% confidence interval has been presented |
| Other |
| Title | Measurements |
|---|---|
|
|
| SBP, To High |
|
| DBP, To Low |
|
| DBP, Within Range or No Change |
|
| DBP, To High |
|
| HR, To Low |
|
| HR, Within Range or No Change |
|
| HR, To High |
|
|
| Hemoglobin,To within Range/No Change, n=27,25,26 |
|
|
| Hemoglobin, To High, , n=27, 25, 26 |
|
|
| Hematocrit, To Low, n=27, 25, 26 |
|
|
| Hematocrit,To within Range/No Change, n=27,25,26 |
|
|
| Hematocrit, To High, n=27, 25, 26 |
|
|
| Lymphocytes, To Low, n=27, 25, 26 |
|
|
| Lymphocytes,To within Range/No Change,n=27,25,26 |
|
|
| Lymphocytes, To High, n=27, 25, 26 |
|
|
| Neutrophil count, To Low, n=27, 25, 26 |
|
|
| Neutrophil,To within Range/No Change, n=27,25,26 |
|
|
| Neutrophil count, To High, n=27, 25, 26 |
|
|
| Platelet count, To Low, n=27, 24, 26 |
|
|
| Platelet,To within Range/No Change,n=27,24,26 |
|
|
| Platelet count, To High, n=27, 24, 26 |
|
|
| WBC, To Low, n=27, 25, 26 |
|
|
| WBC,To within Range/No Change,n=27,25,26 |
|
|
| WBC, To High, n=27, 25, 26 |
|
|
| ALP,To within Range/No Change,n=27, 25, 26 |
|
|
| ALP,To High, n=27, 25, 26 |
|
|
| ALT,To Low, n=27, 25, 26 |
|
|
| ALT,To within Range/No Change, n=27, 25, 26 |
|
|
| ALT,To High, n=27, 25, 26 |
|
|
| AST,To Low, n=26, 25, 26 |
|
|
| AST,To within Range/No Change, n=26, 25, 26 |
|
|
| AST,To High, n=26, 25, 26 |
|
|
| Bilirubin,To Low, n=27, 25, 26 |
|
|
| Bilirubin,To within Range/No Change, n=27, 25, 26 |
|
|
| Bilirubin,To High, n=27, 25, 26 |
|
|
| Calcium,To Low, n=27, 25, 26 |
|
|
| Calcium,To within Range/No Change, n=27, 25, 26 |
|
|
| Calcium,To High, n=27, 25, 26 |
|
|
| Glucose,To Low, n=27, 25, 26 |
|
|
| Glucose,To within Range/No Change, n=27, 25, 26 |
|
|
| Glucose,To High, n=27, 25, 26 |
|
|
| Potassium,To Low, n=27, 25, 26 |
|
|
| Potassium,To within Range/No Change, n=27, 25, 26 |
|
|
| Potassium,To High, n=27, 25, 26 |
|
|
| Sodium,To Low, n=27, 25, 26 |
|
|
| Sodium,To within Range/No Change, n=27, 25, 26 |
|
|
| Sodium,To High, n=27, 25, 26 |
|
|
| BUN,To Low, n=27, 25, 26 |
|
|
| BUN,To within Range/No Change, n=27, 25, 26 |
|
|
| BUN,To High, n=27, 25, 26 |
|
|
|
| Urine Microscopy - Hyaline Casts |
|
| Urine Microscopy - Red Blood Cells |
|
| Urine Microscopy-WBCs (1-9 cells/HPF) |
|