Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Gepotidacin · 13 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.
Blood samples will be collected for the concentrations of gepotidacin
Blood samples will be collected for the concentrations of gepotidacin
Blood samples will be collected for the concentrations of gepotidacin
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)
| 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. |
| Gepotidacin plus Standard of care (SOC) | EXPERIMENTAL | Single Arm |
| Participants receiving gepotidacin powder for oral suspension followed by tablet | EXPERIMENTAL | - |
| Participants receiving gepotidacin tablet followed by powder for oral suspension | EXPERIMENTAL | - |
| 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). |
| 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. |
| 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. |
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...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GSK plc Sponsored ADR | GSK | 2 | PHASE1 | Gepotidacin |
| CorMedix Inc. | CRMD | 1 | PHASE2 | Meropenem-Vaborbactam, Antibiotics |
| Pfizer Inc. | PFE | 1 | - | Undisclosed |
| QIAGEN NV | QGEN | 1 | - | Undisclosed |