Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Change in log10 Colony Forming Units (CFU) Per (/) Milliliter (mL) of Direct Respiratory Sputum Samples From Baseline to Day 14 |
The Early Bactericidal Activity was determined by change in log10CFU/mL of sputum over the period Baseline to Day 14. Log(CFU) was calculated as: Log(CFU/mL)=log10(mean[Total count 1:Total Count 2]*2*5*10^Dilution); where total counts 1 and 2 were bacterial counts from plates 1 and 2 respectively; *2 represents the 1:1 dilution of the original specimen and *5 represents the 0.2 mL (200 microliter) inoculation of the specimen; Dilution is the dilution factor for that plate. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline. |
Baseline and up to Day 14 |
|
Secondary |
Change in log10 CFU/mL of Direct Respiratory Sputum Samples From Baseline to Day 2 |
The Early Bactericidal Activity was determined by change in log10CFU per mL of sputum over the period Baseline to Day 2. Log(CFU) was calculated as: Log(CFU/mL)=log10(mean[Total count 1:Total Count 2]*2*5*10^Dilution); where total counts 1 and 2 were bacterial counts from plates 1 and 2 respectively; *2 represents the 1:1 dilution of the original specimen and *5 represents the 0.2 mL (200 microliter) inoculation of the specimen; Dilution is the dilution factor for that plate. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline. |
Baseline and up to Day 2 |
|
Secondary |
Change in log10 CFU Per mL of Direct Respiratory Sputum Samples From Day 2 to Day 14 |
The Early Bactericidal Activity was determined by change in log10CFU per mL of sputum over the period Day 2 to Day 14. Log(CFU) was calculated as: Log(CFU/mL)=log10(mean[Total count 1:Total Count 2]*2*5*10^Dilution); where total counts 1 and 2 were bacterial counts from plates 1 and 2 respectively; *2 represents the 1:1 dilution of the original specimen and *5 represents the 0.2 mL (200 microliter) inoculation of the specimen; Dilution is the dilution factor for that plate. |
Day 2 to Day 14 |
|
Secondary |
Change in log10 Time to Sputum Culture Positivity (TTP) From Baseline to Day 14 |
The Early Bactericidal Activity was determined by change in TTP per mL sputum over the period Baseline to Day 14. The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) automated liquid culture system of time to positivity of Mycobacterium tuberculosis from an overnight sputum collection. Time to sputum-culture positivity was the time between sample inoculation and detection of mycobacterial growth in the mycobacterium growth indicator tube. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline. |
Baseline and up to Day 14 |
|
Secondary |
Change in log10 TTP From Baseline to Day 2 |
The Early Bactericidal Activity was determined by change in TTP per mL sputum over the period Baseline to Day 2. The TTP was measured in the MGIT automated liquid culture system of time to positivity of Mycobacterium tuberculosis from an overnight sputum collection. Time to sputum-culture positivity was the time between sample inoculation and detection of mycobacterial growth in the mycobacterium growth indicator tube. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline. |
Baseline and up to Day 2 |
|
Secondary |
Change in log10 TTP From Day 2 to Day 14 |
The Early Bactericidal Activity was determined by change in TTP per mL sputum over the period Day 2 to Day 14. The TTP was measured in the MGIT automated liquid culture system of time to positivity of Mycobacterium tuberculosis from an overnight sputum collection. Time to sputum-culture positivity was the time between sample inoculation and detection of mycobacterial growth in the mycobacterium growth indicator tube. |
Day 2 to Day 14 |
|
Secondary |
Area Under the Plasma Drug Concentration Versus Time Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) Following Once Daily Dosing of GSK3036656 |
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3036656. |
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
|
Secondary |
Area Under the Plasma Concentration Time Curve From Zero to 24 Hours (AUC[0-24]) Following Once Daily Dosing of GSK3036656 |
Blood samples were collected at indicated time points for PK analysis of GSK3036656. |
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
|
Secondary |
Maximum Observed Plasma Drug Concentration (Cmax) Following Once Daily Dosing of GSK3036656 |
Blood samples were collected at indicated time points for PK analysis of GSK3036656. |
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
|
Secondary |
Time to Reach Cmax (Tmax) Following Once Daily Dosing of GSK3036656 |
Blood samples were collected at indicated time points for PK analysis of GSK3036656. |
Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
|
Secondary |
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events. |
Up to Day 28 (follow-up visit) |
|
Secondary |
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count |
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils, and platelet count. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Hematology Parameter: Hemoglobin |
Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Hematology Parameter: Hematocrit |
Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Hematology Parameter: Red Blood Cells Count |
Blood samples were collected to analyze the hematology parameter: red blood cells count. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume |
Blood samples were collected to analyze the hematology parameter: mean corpuscular volume. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin |
Blood samples were collected to analyze the hematology parameter: mean corpuscle hemoglobin. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Hematology Parameter: Reticulocytes |
Blood samples were collected to analyze the hematology parameter: reticulocytes. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Potassium, Sodium, Blood Urea Nitrogen |
Blood samples were collected to analyze the chemistry parameters: glucose, calcium, chloride, potassium, sodium, and blood urea nitrogen. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Chemistry Parameters: Lactate Dehydrogenase (LDH), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT) |
Blood samples were collected to analyze the chemistry parameters: LDH, ALT, ALP, AST and GGT. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Chemistry Parameters: Creatinine, Indirect Bilirubin, Direct Bilirubin and Total Bilirubin |
Blood samples were collected to analyze the chemistry parameters: creatinine, indirect bilirubin, direct bilirubin and total bilirubin. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Change From Baseline in Chemistry Parameter: Total Protein |
Blood samples were collected to analyze the chemistry parameter: total protein. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
|
Secondary |
Number of Participants With Worst-Case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method |
Urine samples were collected to assess urine occult blood and urine protein. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased and increase to abnormal for urine occult blood and protein indicating proportional concentrations in the urine sample. 'No change/decreased' means no change from Baseline or a value less than the Baseline value. 'Increase to abnormal' means an increase from the Baseline value that is considered as an abnormal value. Baseline value is the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Data for worst-case post Baseline is presented. |
Baseline (Day 1, Pre-dose) and up to Day 28 (follow-up visit) |
|
Secondary |
Number of Participants With Worst Case Vital Sign Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Vital signs were measured in a semi-supine or supine position after 5 minutes rest. The PCI range for vital signs were: systolic blood pressure (SBP) (lower: <85 and upper: >160 milliliter of mercury [mmHg]); diastolic blood pressure (DBP) (lower: <45 and upper: >100 mmHg); heart rate (lower: <40 and upper: >110 beats per minute [bpm]); respiratory rate (lower: 10 and upper: 28 breaths per minutes) and temperature (lower: <35 and upper: >37.9 degrees Celsius). Participants were counted in the 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 w/in Range or No Change category". Participants were counted twice if the participant had values that changed "To Low" and "To High". |
Up to Day 28 (follow-up visit) |
|
Secondary |
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings |
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, uncorrected QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with abnormal clinically significant ECG findings for worst case post-Baseline has been presented. |
Up to Day 28 (follow-up visit) |
|
Secondary |
Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) |
Twelve-lead ECGs were obtained to QTcF Interval and measured QT duration corrected for heart rate by Fridericia's formula interval. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits and the mean of the triplicate measurements at any given time point was used as the value for that time point. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value. |
Baseline (Day 1, Pre-dose) and at Day 14 |
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