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Tuberculosis remains a concerning health problem, with Mycobacterium Tuberculosis (MTB) now causing more deaths than acquired immune deficiency syndrome (AIDS). GSK3036656 is a compound with a novel mechanism of action under development for the treatment of tuberculosis. It suppresses protein synthesis in MTB by selectively inhibiting the enzyme Leucyl t-ribose nucleic acid (RNA) synthetase. Thus, this study will investigate the early bactericidal activity, safety and tolerability of GSK3036656 in up to four sequential cohorts of subjects with rifampicin-susceptible tuberculosis. The primary objective of this dose-escalation study is to establish the anti-tuberculosis effect of GSK3036656 on serial colony forming units (CFU) counts of MTB in sputum over 14 days of therapy. Subjects in each cohort will be randomized in 3:1 ratio to one of two treatments: either GSK3036656 or standard-of-care (RIFAFOUR® e-275) regimen. The approximate duration of the study for an individual subject will be 5 weeks, including 1 week of screening, 2 weeks of treatment period and another 2 weeks of final follow-up visit. RIFAFOUR e-275 is a registered trademark of Sanofi-Aventis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rifafour e-275 | Active Comparator | All participants will receive a standard-of-care therapy (rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants will receive the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) is completed. |
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| GSK3036656 1 mg | Experimental | Participants will receive a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14. |
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| GSK3036656 5 mg | Experimental | Participants will receive a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14. |
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| GSK3036656 15 mg | Experimental | Participants will receive a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14. |
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| GSK3036656 30 mg | Experimental | Participants will receive a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK3036656 | Drug | GSK3036656 will be administered |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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 | Cape Town | 7530 | South Africa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38365949 | Derived | Diacon AH, Barry CE 3rd, Carlton A, Chen RY, Davies M, de Jager V, Fletcher K, Koh GCKW, Kontsevaya I, Heyckendorf J, Lange C, Reimann M, Penman SL, Scott R, Maher-Edwards G, Tiberi S, Vlasakakis G, Upton CM, Aguirre DB. A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial. Nat Med. 2024 Mar;30(3):896-904. doi: 10.1038/s41591-024-02829-7. Epub 2024 Feb 16. | |
| 35876255 |
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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 76 participants were enrolled (Enrolled Population consisted of all participants who passed screening and entered the study) in this study.
This was an open-label trial to investigate the early bactericidal activity, safety and tolerability of GSK3036656 in participants with drug-sensitive pulmonary tuberculosis. Participants received Rifafour e-275 as a standard-of-care or GSK3036656. Rifafour e-275 is a registered trademark of Sanofi-Aventis company.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rifafour e-275 | All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed. |
| FG001 | GSK3036656 1 mg | Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14. |
| FG002 | GSK3036656 5 mg | Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14. |
| FG003 | GSK3036656 15 mg | Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14. |
| FG004 | GSK3036656 30 mg | Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safety Population consisted of all randomized participants who received at least one dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Rifafour e-275 | All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
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| 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 | 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. | Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. | Posted | Mean | Standard Error | Log10CFU/mL | Baseline and up to Day 14 |
|
All-cause mortality, SAEs and non-SAEs were collected up to Day 28 (follow-up visit)
Safety Population consisted of all randomized participants who received at least one dose of study treatment.
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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 | Rifafour e-275 | All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 12, 2021 | Nov 16, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 1, 2022 | Nov 16, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D014397 | Tuberculosis, Pulmonary |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
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| ID | Term |
|---|---|
| C000624292 | GSK656 |
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Eligible subjects in each cohort will be randomized to receive sequential doses of either GSK3036656 or standard-of-care (RIFAFOUR) regimen. This study will employ dose escalation, where the decision to proceed to each subsequent dose level will be made based on safety, tolerability and preliminary pharmacokinetic data from the prior cohort.
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This will be an open label study. Hence, there will be no masking.
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|
| Rifafour e-275 | Drug | Rifafour e-275 will be administered |
|
| Baseline and up to Day 2 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| 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) |
| 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 |
| Derived |
| Volynets GP, Usenko MO, Gudzera OI, Starosyla SA, Balanda AO, Syniugin AR, Gorbatiuk OB, Prykhod'ko AO, Bdzhola VG, Yarmoluk SM, Tukalo MA. Identification of dual-targeted Mycobacterium tuberculosis aminoacyl-tRNA synthetase inhibitors using machine learning. Future Med Chem. 2022 Sep;14(17):1223-1237. doi: 10.4155/fmc-2022-0085. Epub 2022 Jul 25. |
| Withdrawal by Subject |
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| Randomized, but did not receive treatment |
|
| GSK3036656 1 mg |
Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14. |
| BG002 | GSK3036656 5 mg | Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14. |
| BG003 | GSK3036656 15 mg | Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14. |
| BG004 | GSK3036656 30 mg | Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14. |
| BG005 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed. |
| OG001 | GSK3036656 1 mg | Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14. |
| OG002 | GSK3036656 5 mg | Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14. |
| OG003 | GSK3036656 15 mg | Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14. |
| OG004 | GSK3036656 30 mg | Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 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. | Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Error | log10CFU/mL | Baseline and up to Day 2 |
|
|
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| 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. | Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Error | log10CFU/mL | 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. | Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. | Posted | Mean | Standard Error | log10hours | 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. | Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. | Posted | Mean | Standard Error | log10hours | Baseline and up to Day 2 |
|
|
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| 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. | Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Error | log10hours | Day 2 to Day 14 |
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| 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. | PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
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| 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. | PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
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| 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. | PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
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| 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. | PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed. | Posted | Median | Full Range | Hours | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to Day 28 (follow-up visit) |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Grams per liter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Proportion of red blood cells in blood | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | 10^12 cells per liter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Femtoliter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Picograms | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Percentage of reticulocytes | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Millimoles per liter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | International units per liter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Grams per liter | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Baseline (Day 1, Pre-dose) and up to Day 28 (follow-up visit) |
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| 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". | Safety Population consisted of all randomized participants who received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to Day 28 (follow-up visit) |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Count of Participants | Participants | Up to Day 28 (follow-up visit) |
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| 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. | Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed. | Posted | Mean | Standard Deviation | Milliseconds | Baseline (Day 1, Pre-dose) and at Day 14 |
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| 0 |
| 18 |
| 0 |
| 18 |
| 14 |
| 18 |
| EG001 | GSK3036656 1 mg | Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14. | 0 | 9 | 0 | 9 | 7 | 9 |
| EG002 | GSK3036656 5 mg | Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14. | 0 | 17 | 0 | 17 | 14 | 17 |
| EG003 | GSK3036656 15 mg | Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14. | 0 | 16 | 0 | 16 | 15 | 16 |
| EG004 | GSK3036656 30 mg | Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14. | 0 | 15 | 0 | 15 | 9 | 15 |
| Dyspepsia | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Odynophagia | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Skin hypopigmentation | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Blister | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Carbuncle | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Fungal skin infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Otitis externa | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Pulmonary tuberculosis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Tinea versicolour | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA 24.1 | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA 24.1 | Systematic Assessment |
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| Uveitis | Eye disorders | MedDRA 24.1 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 24.1 | Systematic Assessment |
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| Ejection fraction decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
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| Electrocardiogram PR prolongation | Investigations | MedDRA 24.1 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 24.1 | Systematic Assessment |
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| Ventricular hypokinesia | Cardiac disorders | MedDRA 24.1 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDRA 24.1 | Systematic Assessment |
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| Noninfective myringitis | Ear and labyrinth disorders | MedDRA 24.1 | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 24.1 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 24.1 | Systematic Assessment |
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| Hypersensitivity | Immune system disorders | MedDRA 24.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 24.1 | Systematic Assessment |
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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.
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| SAEs1 |
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| Eosinophils |
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| Lymphocytes |
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| Monocytes |
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| Total neutrophils |
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| Platelet count |
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| Calcium |
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| Chloride |
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| Potassium |
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| Sodium |
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| Blood urea nitrogen |
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| ALT |
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| ALP |
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| AST |
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| GGT |
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| Indirect bilirubin |
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| Direct bilirubin |
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| Total bilirubin |
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| Occult blood: Increase to abnormal |
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| Protein: No change/decrease |
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| Protein: Increase to abnormal |
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| SBP: To within Range or No Change |
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| SBP: To High |
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| DBP: To low |
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| DBP: To within Range or No Change |
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| DBP: To High |
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| Heart rate: To low |
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| Heart rate: To within Range or No Change |
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| Heart rate: To High |
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| Respiratory rate: To low |
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| Respiratory rate: To within Range or No Change |
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| Respiratory rate: To High |
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| Temperature: To low |
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| Temperature: To within Range or No Change |
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| Temperature: To High |
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| Abnormal - clinically significant |
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