Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GSK2140944 (Single dose), GSK2140944 capsule, GSK2140944 for Injection, GSK2140944 Capsules, Gepotidacin
GSK2140944 · 19 trials · 4 indications
Clinical Symptom improvement is defined as a decrease from Baseline in CSS (Clinical Symptom Score) total score of at least 1 point at 24 hours (±4 hours), without the need for other systemic antimicrobials. CSS Score ranges from 0 to 12. Higher scores indicate a higher presence and severity of UTI symptoms.
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at Baseline \[BL\] to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at Baseline \[BL\] to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
Urogenital specimens were obtained for bacteriological culture at the Baseline (Day 1) and TOC (Day 4 to 8) visits and were compared to determine microbiological outcome. Microbiological success was defined as culture-confirmed elimination of baseline pathogen (NG) from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. Microbiological failure was categorized as "Bacterial Persistence (BP)" and "Unable to Determine (UTD)" outcomes. Bacterial persistence was defined as culture-confirmed persistence of baseline NG pathogen from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. UTD was defined as inability to determine the TOC NG pathogen outcome (e.g., no bacteriological sample taken for culture, sample lost, visit did not occur etc.) or the participant received other systemic antimicrobials before the TOC visit.
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population consisted of all participants who received gepotidacin 1500 mg BID through the completion of all PK collections for whom valid and evaluable plasma PK parameters were derived for gepotidacin.
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. CLss/F was calculated as Dose divided by AUC(0-tau).
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Accumulation ratio (Ro) was calculated as ratio of AUC(0-tau) at Day 4 to AUC(0-tau) at Day 1.
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Pre-treatment urogenital, pharyngeal, and rectal swab specimens were obtained for bacteriological culture for neisseria (N.) gonorrhoeae at the Baseline visit. Test- of-Cure was defined by infection site (that is urogenital and, as appropriate, rectal and/or pharyngeal) as culture confirmed bacterial eradication of N. gonorrhoeae observed 3 to 7 days post-treatment. Pre-treatment urogenital specimens were obtained for nucleic acid amplification test (NAAT) assay to detect the presence of N. gonorrhoeae and chlamydia trachomatis at the Baseline visit. Only participants who had a pre-therapy N. gonorrhoeae isolate recovered from their urogenital specimen were evaluated. Microbiologically evaluable (ME) Population comprised of all randomized participants who had N. gonorrhoeae isolated from Baseline cultures of urogenital swab specimens, received any dose of gepotidacin, and returned for their TOC visit.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
An adverse event (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. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal 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 normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis
Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is 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. Number of participants with common (\>=5%) non-serious AEs and SAEs is presented.
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. An SAE is 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. Number of participants with common (\>=5%) non-serious AEs and SAEs are presented.
Blood samples were collected for the analysis of following hematology parameters: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. The hematology abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the hematology parameter is presented.
Blood samples were collected for the analysis of following hematology parameters: platelet count, RBC count, hemoglobin, hematocrit, MCV, MCH, WBC count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. The hematology abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the hematology parameter is presented.
Blood samples were collected for the analysis of following clinical chemistry parameters: blood urea nitrogen (BUN), creatinine, glucose (fasting), potassium, sodium, magnesium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total and direct bilirubin, creatine phosphokinase, calcium, chloride, carbon dioxide, total protein and albumin. The clinical chemistry abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the clinical chemistry parameter is presented
Blood samples were collected for the analysis of following clinical chemistry parameters: BUN, creatinine, glucose (fasting), potassium, sodium, magnesium, AST, ALT, alkaline phosphatase, total and direct bilirubin, creatine phosphokinase, calcium, chloride, carbon dioxide, total protein and albumin. The clinical chemistry abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the clinical chemistry parameter is presented
Urine samples were collected for the analysis of urine parameters including specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase. Toxicities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the urine parameter is presented
Urine samples were collected for the analysis of urine parameters including specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase. Toxicities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the urine parameter is presented
SBP and DBP were measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for vital signs were: SBP (lower: \<85 and upper: \>160 millimeters of mercury \[mmHg\]) and DBP (lower: \<45 and upper: \>100 mmHg).
SBP and DBP were measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for vital signs were: SBP (lower: \<85 and upper: \>160 mmHg) and DBP (lower: \<45 and upper: \>100 mmHg).
Heart rate was measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for heart rate was (lower:\<40 and upper: \>110 beats per minute).
Heart rate was measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for heart rate was (lower:\<40 and upper: \>110 beats per minute).
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and corrected QT (QTc) intervals and calculated heart rate. Data for abnormal not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal 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.
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS ECG findings are presented. CS abnormal 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.
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS ECG findings are presented. CS abnormal 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.
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS were presented. CS abnormal 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.
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS were presented CS abnormal 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.
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters. PK parameter population consist of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. This population was used in the assessment and characterization of PK parameters.
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity . Blood samples were collected at the indicated time-points, during the study. The Pharmacokinetic (PK) Parameter Population consisted of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. The PK Population consisted of all participant's, who received at least 1 dose of gepotidacin and had evaluable PK data.
AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for gepotidacin. Blood samples were collected at the indicated time-points, during the study.
Cmax, is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected, at the indicated time points for analysis of gepotidacin.
Cmax, is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected, at the indicated time points for analysis of gepotidacin.
Urine samples from the participants were collected during the study. Ae total assessed the, total unchanged drug (total amount of drug excreted in urine), which was calculated, by adding all the fractions of drug gepotidacin collected, at the indicated time points. No formal statistical analysis of group comparison was planned for urine PK parameters.
Urine samples, from the participants were collected during the study. Ae total assessed the, total unchanged drug (total amount of drug excreted in urine), which was calculated, by adding all the fractions of drug gepotidacin collected, at the indicated time points. Urine samples were collected at pre-dose (0.0), 0 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period. Only those participant's available at the specified time points were analyzed. No formal statistical analysis of group comparison was planned for urine PK parameters.
The fe% measured the percentage of the given dose of drug gepotidacin, excreted in urine. It was calculated as: Ae total divided by the dose administered multiplied by 100.
The fe% measured the percentage of the given dose of drug gepotidacin, excreted in urine. It was calculated as: Ae total divided by the dose administered multiplied by 100. No formal statistical analysis of group comparison was planned for urine PK parameters. Only those participants available at the specified time points were analyzed.
Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time via renal clearance pathways, expressed as volume (Liter) per unit of time (hour). The renal clearance was calculated by Ae total divided by AUC from hour 0 to the last measurable plasma concentration AUC (0-t). Urine samples were collected at pre-dose (0.0), 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose during the single treatment period. No formal statistical analysis of group comparison was planned for urine PK parameters.
Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time via renal clearance pathways, expressed as volume (Liter) per unit of time (hour). Urine samples were collected at pre-dose (0.0), 0 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours post-dose in each of the two treatment periods. Only those participant's available at the specified time points were analyzed. No formal statistical analysis of group comparison was planned for urine PK parameters.
Partial area under the curve estimated from predialyzer samples collected from start of dialysis (t0) to end of dialysis (t1). Only applicable to Part 2 ESRD on hemodialysis (before hemodialysis) arm..
CLD measured the dialysis clearance of gepotidacin over the specified duration in the study and indicates how quickly gepotidacin is cleared out from blood or plasma. Only applicable to Part 2 ESRD on hemodialysis (before hemodialysis) arm.
Dialysate samples were collected at specified time points in the study. Frem is defined as the fraction (dose in percentage) removed by the process of hemodialysis from 0 to 4 hours after the start of hemodialysis (or to the end of dialysis if less than 4 hours)
ECGs will be measured using a 24-hour continuous 12-lead Holter monitor. ECGs will be extracted up to 10 replicates at the following time points: at 3 time points pre-dose (45, 30, and 15 minutes prior to starting the infusion) and 0.25, 0.5, 1.0, 1.5, 2.0 (end of infusion), 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24 and 48 hours after dosing, for a total of 16 time points per treatment period
PK parameters will include area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time AUC(0-infinity), AUC from time zero to last quantifiable concentration AUC(0-t), relative bioavailability of drug (Frel), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), lag time before observation of drug concentration (tlag) and terminal phase half-life (t1/2) in the fasted state; AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax after moderate fat meal.
PK parameters will include AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax of GSK2140944.
Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes
Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature
From the plasma concentration-time and blood/plasma radioactivity concentration-time data, the following pharmacokinetic parameters will be determined, as data permit: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve \[AUC(0-t) and AUC(0-∞)\], and apparent terminal phase half-life (t1/2). Systemic clearance (CL) and volume of distribution (Vdss) of GSK2140944 may be calculated for IV regimen only.
Total recovery of radioactivity in urine and feces is defined as a percentage of total radioactive dose in each interval and cumulatively.
Blood samples will be collected assessment of PK parameters including Epithelial Lining Fluid (ELF) and Alveolar Macrophages (AM) (AUC\[0- τ\]), Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a participant across all treatments (AUC\[0-t\]), Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
Blood samples will be collected assessment of PK parameters including ELF and AM AUC(0- τ)), AUC(0-t), Cmax, tmax, ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
12-lead ECGs will be obtained at each timepoint using an ECG machine, after the subject has rested in a semi-supine position for at least 10 minutes
Continuous dual-lead cardiac monitoring will be obtained at each timepoints using an ECG machine
Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters
Safety and tolerability parameters will include recording of AEs, throughout the study
Vital sign measurements will be done in semi-supine position and will include systolic and diastolic blood pressure
Vital sign measurements will be done in semi-supine position and will include pulse rate
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 12 hour post-dose (AUC(0-12)) following single dose of GSK2140944
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 24 hour post-dose (AUC(0-24)) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)) following single dose of GSK2140944
Pharmacokinetic data will include maximum observed concentration (Cmax) following single dose of GSK2140944
Pharmacokinetic data will include time of occurrence of Cmax (tmax) following single dose of GSK2140944
Pharmacokinetic data will include terminal phase half-life (t1/2) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve over the dosing interval (AUC(0-tau)) following repeat dose of GSK2140944
Pharmacokinetic data will include Cmax following repeat dose of GSK2140944
Pharmacokinetic data will include tmax following repeat dose of GSK2140944
Pharmacokinetic data will include pre-dose (trough) concentration at the end of the dosing interval (Ctau) following repeat dose of GSK2140944
Pharmacokinetic data will include accumulation ratio (Ro) following repeat dose of GSK2140944
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 8 hour post-dose (AUC\[0-8\]) following single dose of GSK2140944
| Arm | Type | Description |
|---|---|---|
| Gepotidacin | EXPERIMENTAL | Single Arm |
| Gepotidacin + Placebo | EXPERIMENTAL | - |
| Nitrofurantoin + Placebo | ACTIVE_COMPARATOR | - |
| Nitrofurantoin | ACTIVE_COMPARATOR | Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days. |
| Participants receiving Gepotidacin | EXPERIMENTAL | Participants will receive Gepotidacin orally at the study site during the Baseline (Day 1) visit followed by self-administration of a second oral dose as an outpatient 10 to 12 hours after the first dose. |
| Participants receiving Ceftriaxone plus Azithromycin | ACTIVE_COMPARATOR | Participants will receive a single IM dose of Ceftriaxone plus a single oral dose of Azithromycin at the study site during the Baseline (Day 1) visit. |
| Female subjects with acute cystitis | EXPERIMENTAL | Adult female subjects with suspected acute cystitis based on clinical presentation and pyuria (\>=10 WBC/mm\^3 or presence of leukocyte esterase) and/or nitrite will be included. Subjects will be administered 1500 mg gepotidacin BID for 5 days via the oral route. |
| GSK2140944 1500 mg | EXPERIMENTAL | Subjects will receive single oral dose of GSK2140944 1500 mg. |
| GSK2140944 3000 mg | EXPERIMENTAL | Subjects will receive single oral dose of GSK2140944 3000 mg. |
| Gepotidacin plus Standard of care (SOC) | EXPERIMENTAL | Single Arm |
| Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg | EXPERIMENTAL | This is a fixed sequence (Sequence AB) cohort. Participants will receive gepotidacin 1500 milligrams (mg) single dose (SD) on Day 1 of Period 1 (Treatment A); and Cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 and gepotidacin 1500 mg single dose (Treatment B). Gepotidacin will be administered 1 hour after the first dose of cimetidine on Day 2 of Period 2. There will be a washout of at least 3 days between Treatment A and Treatment B, and a follow-up visit 5 to 7 days after the last dose of cimetidine. |
| Cohort 2: Gepotidacin 1500 mg + Rifampicin 600 mg | EXPERIMENTAL | This is a fixed sequence (Sequence CDE) cohort. Participants will receive gepotidacin 1500 mg single dose on Day 1 of Period 1 (Treatment C), rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7 of Period 2, to elicit maximal enzyme induction) (Treatment D); and gepotidacin 1500 mg single dose administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 (Treatment E). There will be a washout of at least 3 days between Treatment C and Treatment D, and a follow-up visit 7 to 10 days after the last dose of rifampicin. |
| Cohort 3: Digoxin 0.5mg+Midazolam 2mg then Gepotidacin 3000mg | EXPERIMENTAL | Participants will receive digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 1 on Day 1 then gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 2 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G). There will be a washout of at least 10 days between treatments. In Sequence 2, these regimens are reversed. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2. |
| Cohort 3: Gepotidacin 3000mg then Digoxin 0.5mg+Midazolam 2mg | EXPERIMENTAL | Participants will receive gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 1 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G) followed by digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 2 on Day 1. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2. |
| Cohort 4: Gepotidacin 1500 mg fed then fasted then 3000 mg fed | EXPERIMENTAL | Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fed conditions in Period 1 (Treatment H), then a single dose of gepotidacin 1500 mg under fasted conditions in Period 2 (Treatment I), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin. |
| Cohort 4: Gepotidacin 1500 mg fasted then fed then 3000 mg fed | EXPERIMENTAL | Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fasted conditions in Period 1 (Treatment I), then a single dose of gepotidacin 1500 mg under fed conditions in Period 2 (Treatment H), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin. |
| Cohort 4: Placebo fed then fasted then fed | PLACEBO_COMPARATOR | Cohort 4 will include Japanese participants. Participants will receive a single dose of placebo under fed conditions in Period 1, then a single dose of placebo under fasted conditions in Period 2, followed by two doses of placebo (given 12 hours apart) under fed conditions in Period 3. There will be a washout of at least 3 days between each period, and a follow-up visit 5 to 7 days after the last dose of placebo. |
| Subjects receiving Gepotidacin in Part 1 | EXPERIMENTAL | Healthy adult subjects will receive a single oral dose of gepotidacin 1500 mg (2 X 750 mg, treatment A), tablets, on Day 1 of Period 1; two oral doses of gepotidacin 3000 mg (4 x 750 mg, Treatment C), tablets, at 0 and 12 hours on Day 5 of Period 2; and two oral doses of gepotidacin 3000 mg (4 x 750 mg, treatment E), tablets, at 0 and 6 hours on Day 9 of Period 3. |
| Subjects receiving Placebo in Part 1 | PLACEBO_COMPARATOR | Healthy adult subjects will receive a single oral dose of matching placebo (treatment B), tablets, on Day 1 of Period 1; two oral doses of matching placebo (treatment D), tablets, at 0 and 12 hours on Day 5 of Period 2; and two oral doses of matching placebo (treatment F), tablets, at 0 and 6 hours on Day 9 of Period 3. |
| Subjects receiving Gepotidacin in Part 2 | EXPERIMENTAL | Healthy adolescent subjects will receive a single oral dose of gepotidacin 1500 mg (2 x 750 mg, treatment A), tablets, on Day 1 of Period 1; and two oral doses of gepotidacin 3000 mg (4 x 750 mg, treatment G), tablets, at 0 and 6 hours on Day 1 of Period 2. |
| Subjects receiving Placebo in Part 2 | PLACEBO_COMPARATOR | Healthy adolescent subjects will receive a single oral dose of matching placebo (treatment B), tablets on Day 1 of Period 1; and two oral doses of matching placebo (treatment H), tablets at 0 and 6 hours on Day 1 of Period 2. |
| Normal Hepatic function, Part 1 (Group D) | EXPERIMENTAL | The eligible subjects, with normal hepatic function, in this arm will receive a single oral dose of gepotidacin as 1500 milligram (mg), administered as 2 × 750 mg tablets on Day 1. |
| Moderate hepatic impairment, Part 1 (Group B) | EXPERIMENTAL | The subjects in this arm, will be the one's with a Child-Pugh score of 7 to 9, and will receive a single oral dose of gepotidacin, as 1500 mg, administered as 2 × 750 mg tablets on Day 1. |
| Mild hepatic impairment, Part 2 (Group A) | EXPERIMENTAL | The subjects in this arm, will be the one's with a Child-Pugh score of 5 to 6, and will receive a single oral dose of gepotidacin, as 1500 mg, administered as 2 × 750 mg tablets on Day 1. This will be optional arm. |
| Severe hepatic impairment, Part 2 (Group C) | EXPERIMENTAL | The subjects in this arm, will be the one's, with a Child-Pugh score of 7 to 9, and will receive a single oral dose of gepotidacin, as 1500 mg, administered as 2 × 750 mg tablets, on Day 1. |
| Normal Hepatic function, Part 2 (Group E) | EXPERIMENTAL | The eligible subjects, with normal hepatic function, will be matching with those enrolled in Part1, and will receive a single oral dose of gepotidacin as 1500 mg, administered as 2 × 750 mg tablets on Day 1. |
| Part 1: Subjects with normal renal function (Group A) | EXPERIMENTAL | Subjects with normal renal function will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion. |
| Part 1: subjects with moderate renal impairment (Group B) | EXPERIMENTAL | Subjects with moderate renal impairment will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion. |
| Part 1: subjects with severe renal impairment (Group C) | EXPERIMENTAL | Subjects with severe renal impairment and subjects with ESRD not on hemodialysis will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion. |
| Part 2: subjects with normal renal function (Group D) | EXPERIMENTAL | Subjects with normal renal function will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion. |
| Part 2: subjects with mild renal impairment (Group E) | EXPERIMENTAL | Subjects with mild renal impairment will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion. |
| Part 2: subjects with ESRD on hemodialysis (Group F) | EXPERIMENTAL | Subjects with ESRD on hemodialysis will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (Period 1) and gepotidacin 750 mg administered as a 2 hour IV infusion starting within 2 hours after completion of the last hemodialysis session of the week (Period 2). |
| Sequence ABDC | EXPERIMENTAL | Subjects will be administered treatments in Sequence ABDC where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Sequence BCAD | EXPERIMENTAL | Subjects will be administered treatments in Sequence BCAD where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Sequence CDBA | EXPERIMENTAL | Subjects will be administered treatments in Sequence CDBA where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Sequence DACB | EXPERIMENTAL | Subjects will be administered treatments in Sequence DACB where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Part 1 | EXPERIMENTAL | Subjects will receive either GSK2140944 1500 mg (500 mg x 3) capsules under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fed conditions as per the randomization schedule in each of the three periods with a washout period of at least 3 days between the doses. There will also be a follow-up visit within 5-7 days after the last dose of study drug. |
| Part 2 | EXPERIMENTAL | Subjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) on Day 1 followed by a repeat dose of Itraconazole 200 mg once daily for 6 days from Day 4 to Day 9. On Day 7, subjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) one hour after the dose of Itraconazole. There will also be a follow-up visit within 5-7 days after the last dose of study drug. |
| Part 3 | EXPERIMENTAL | Subjects in Group 1 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fasting and fed conditions in Period I and Period II, respectively. Subjects in Group 2 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fed and fasting conditions in Period I and Period II, respectively. There will be a washout of at least 7 days between the periods. Subjects will have a follow up visit 5-7 days after the last dose of study drug in both the groups. |
| GSK2140944 for Injection and Capsule | EXPERIMENTAL | Each subject will receive a single 1000 milligram (mg) IV dose of GSK2140944 containing \[14C\]-GSK2140944 of approximately 22.5 microcurie \[μCi\] (approximately 0.8 megabecquerel \[MBq\]) of radioactivity given as a 2 hour infusion on Day 1 of treatment period 1 and 2000 mg oral dose of GSK2140944 containing \[14C\]-GSK2140944 of approximately 45 μCi (approximately 1.7 MBq) of radioactivity on Day 1 of treatment period 2. Each treatment period will be followed with washout of atleast 8 Days. |
| Part A(Cohort1) | EXPERIMENTAL | Study BTZ116666 has two parts. Each part will consist of a maximum of 6 cohorts. Part A will be initiated with 4 initial cohorts/timepoints in order to minimize the number of healthy volunteers that undergo bronchoscopy in this study. After review of data from Cohorts 1 through 4 of Part A, the study team will determine if additional cohorts are needed to be studied in Part A and/ or if Part B is needed. If the study team determines that additional cohorts are needed, then only the necessary cohorts in Parts A and/or B will be executed. In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 2 hours x 1 dose |
| Part A (Cohort2) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 4 hours x 1 dose |
| Part A (Cohort3) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 8 hours x 1 dose |
| Part A (Cohort4) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 12 hours x 1 dose |
| Part A (Cohort5) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part A (Cohort6) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort1) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort2) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort3) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort4) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort5) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort6) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Cohort 1 - GSK2140944 400 mg | EXPERIMENTAL | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days |
| Cohort 1 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days |
| Cohort 2 - GSK2140944 800 mg | EXPERIMENTAL | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 2 will be decided based on the safety and PK data from six subjects in Cohort 1 |
| Cohort 2 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days |
| Cohort 3 - GSK2140944 1500 mg | EXPERIMENTAL | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 3 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 2 |
| Cohort 3 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days |
| Cohort 4 - GSK2140944 2500 mg | EXPERIMENTAL | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 4 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 3 |
| Cohort 4 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days |
| Cohort 5 - GSK2140944 TBD | EXPERIMENTAL | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 4 |
| Cohort 5 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days |
| Cohort 6 - GSK2140944 TBD | EXPERIMENTAL | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 6 subjects dosed at the Cohort 5 |
| Cohort 6 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days |
| GSK2140944 | EXPERIMENTAL | Dose range 100mg to 3000mg single dose |
| Matching Placebo | PLACEBO_COMPARATOR | Placebo |
| Name | Type | Description |
|---|---|---|
| Gepotidacin | DRUG | Gepotidacin will be administered. |
| Nitrofurantoin | DRUG | Nitrofurantoin will be administered. |
| Placebo | DRUG | Placebo will be administered. |
| Placebo matching nitrofurantoin | DRUG | Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Participants will administer 1 capsule BID. Each dose should be taken with water after consumption of food. |
| Placebo matching gepotidacin | DRUG | Placebo matching gepotidacin will be available as unit-dose gepotidacin placebo-to-match tablet. Participants will administer two tablets, BID. Each dose should be taken with water after consumption of food. |
| Ceftriaxone | DRUG | Ceftriaxone is available as sterile powder for reconstitution. It will be administered as one 500-mg IM dose at the study site. |
| Azithromycin | DRUG | Azithromycin will be administered as 1000 mg oral dose (2 X 500 mg tablets) at the study site. Dose should be taken after food consumption and with water. |
| GSK2140944 | DRUG | Immediate release capsules (pink hard gelatin size 00 capsule, with no external marking, filled with slightly agglomerated pale yellowish to grayish yellow powder) containing GSK2140944 500 mg and inactive formulation excipients. GSK2140944 will be administered orally once 1500 mg (3 capsules) or 3000 mg (6 capsules). |
| SOC | DRUG | SOC will be administered |
| Cimetidine | DRUG | Cimetidine tablets will be available as unit dose strength 400 mg and will be administered orally. |
| Rifampicin | DRUG | Rifampicin Capsules will be available as unit dose strength 300 mg and will be administered orally. |
| Midazolam | DRUG | Midazolam oral syrup 2 milligrams per milliliter (mg/mL) will be available to be administered orally. |
| Digoxin | DRUG | Digoxin tablets will be available as unit dose strength 0.25 mg and will be administered orally. |
| Placebo matching to gepotidacin | OTHER | Placebo matching to gepotidacin tablets will be administered orally. |
| GSK2140944 placebo | DRUG | GSK2140944 placebo is 0.9% sodium chloride available for single IV dose over 2 hours administration. |
| Moxifloxacin | DRUG | Moxifloxacin is available as pinkish red tablet with dose strength 400 mg for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water. |
| Moxifloxacin placebo | DRUG | Moxifloxacin placebo is available as white, film-coated tablet. containing nonactive material for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water. |
| GSK2140944 capsule | DRUG | Immediate release capsule containing GSK2140944 and inactive formulation excipients with a unit dose strength of 500 mg |
| GSK2140944 tablet | DRUG | Immediate release tablet containing GSK2140944 and inactive formulation excipients with a unit dose strength of 750 mg |
| Itraconazole capsule | DRUG | Capsule containing Itraconazole with a unit dose strength of 100 mg |
| GSK2140944 for Injection | DRUG | GSK2140944 (1 gram) for Injection will be supplied as powder for injection containing \[14C\] GSK2140944. Non sterile powder is to be dissolved aseptically in sterile water for injection to a concentration of 4 mg/mL free base equivalent. IV solution is prepared by sterile filtration. 250 mL of IV solution, equivalent to 1000 mg GSK2140944, is then administered intravenously. |
| GSK2140944 (Single dose) | DRUG | A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose. |
| GSK2140944 (Multiple dose) | DRUG | A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days). |
Inclusion Criteria: * Participants having \>=12 years of age at the time of signing the informed consent/assent and have a body weight \>=40 kilograms (kg). * The participant has 2 or more of the following clinical signs and symptoms of acute cystitis with onset \<96 hours prior to study entry: dys...
GSK2140944 is an investigational antibacterial being studied for the treatment of uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae, as well as for bacterial and respiratory tract infections. It is a small molecule developed by GSK plc and has been tested in Phase 2 and Phase 1 clinical trials.
GSK2140944 is developed by GSK plc, which trades under the ticker GSK. The company sponsored all four registered clinical trials of the drug, including the Phase 2 dose-ranging study in gonorrhea and three Phase 1 studies in healthy volunteers.
GSK2140944 has completed Phase 2 development. Its most advanced trial was a Phase 2 dose-ranging study in uncomplicated urogenital gonorrhea, and three Phase 1 studies have also been completed. No trials are currently active, and the drug is not approved.
GSK2140944 has been evaluated in four completed trials: NCT02294682, a Phase 2 dose-ranging study in uncomplicated urogenital gonorrhea; NCT02257398, a Phase 1 cardiac conduction study; NCT02202187, a Phase 1 single oral escalating dose study; and NCT02045849, a Phase 1 bioavailability and food effect study.
Yes, GSK2140944 capsule, GSK2140944 for Injection, GSK2140944 Capsules, and GSK2140944 (Single dose) are all alternative names for the same investigational drug, GSK2140944. These names reflect different formulations or dosing presentations studied under the same development program.