Pharmacokinetic Study of Gepotidacin in Subjects With Varying Degrees of Renal Impairment and in Subjects With Normal Renal Function

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02729038
• Collaborator: (none)
• Enrollment: 32
• Locations: 3
• Arms: 6
• Actual Duration (Months): 11.7
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study will be conducted to determine if altered renal function affects the plasma pharmacokinetics of gepotidacin, which will inform if dosing recommendations based upon renal impairment are required. The objective of this study is to compare the pharmacokinetics of gepotidacin administered as a 750 milligram (mg) intravenous (IV) dose in normal healthy subjects compared with subjects with mild, moderate, and severe renal impairment, and with subjects with end stage renal disease (ESRD). This is a Phase I, nonrandomized, open-label, parallel-group, multi-center, multi-part study. In Part 1, up to 16 subjects with normal renal function will be matched to approximately 8 subjects with moderate renal impairment, and approximately 8 subjects with severe renal impairment and/or subjects with ESRD not on hemodialysis for a total of approximately 32 subjects. In Part 2 (optional), approximately 4 to 8 subjects with normal renal function (if enrolled), approximately 4 to 8 subjects with mild renal impairment, and approximately 4 to 8 subjects with ESRD on hemodialysis will be enrolled for a total of approximately 12 to 24 subjects. The duration from Screening to the Follow-up Visit will be approximately 44 days for Part 1 and approximately 50 days for Part 2.

Condition or Disease	Intervention/Treatment	Phase
Infections, Bacterial	Drug: Gepotidacin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Open-Label, Single-Dose, Multi-Part Study to Assess the Pharmacokinetics of Gepotidacin (GSK2140944) in Male and Female Adult Subjects With Varying Degrees of Renal Impairment and in Matched Control Subjects With Normal Renal Function
• Actual Study Start Date: Jun 29, 2016
• Actual Primary Completion Date: Jun 20, 2017
• Actual Study Completion Date: Jun 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Subjects with normal renal function (Group A) Subjects with normal renal function will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion.	Drug: Gepotidacin; Gepotidacin after reconstitution is a clear, dark brown to dark brownish-yellow solution, free from visible particulate matter. Subjects will receive gepotidacin 750 mg single IV dose over 2 hours.
Experimental: Part 1: subjects with moderate renal impairment (Group B) Subjects with moderate renal impairment will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion.	Drug: Gepotidacin; Gepotidacin after reconstitution is a clear, dark brown to dark brownish-yellow solution, free from visible particulate matter. Subjects will receive gepotidacin 750 mg single IV dose over 2 hours.
Experimental: Part 1: subjects with severe renal impairment (Group C) 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.	Drug: Gepotidacin; Gepotidacin after reconstitution is a clear, dark brown to dark brownish-yellow solution, free from visible particulate matter. Subjects will receive gepotidacin 750 mg single IV dose over 2 hours.
Experimental: Part 2: subjects with normal renal function (Group D) Subjects with normal renal function will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion.	Drug: Gepotidacin; Gepotidacin after reconstitution is a clear, dark brown to dark brownish-yellow solution, free from visible particulate matter. Subjects will receive gepotidacin 750 mg single IV dose over 2 hours.
Experimental: Part 2: subjects with mild renal impairment (Group E) Subjects with mild renal impairment will receive a single dose of gepotidacin 750 mg administered as a 2 hour IV infusion.	Drug: Gepotidacin; Gepotidacin after reconstitution is a clear, dark brown to dark brownish-yellow solution, free from visible particulate matter. Subjects will receive gepotidacin 750 mg single IV dose over 2 hours.
Experimental: Part 2: subjects with ESRD on hemodialysis (Group F) 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).	Drug: Gepotidacin; Gepotidacin after reconstitution is a clear, dark brown to dark brownish-yellow solution, free from visible particulate matter. Subjects will receive gepotidacin 750 mg single IV dose over 2 hours.

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

   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.

2. AUC (0-inf) of Gepotidacin for Part 2 [Pre-dose, 0.25 hours, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.]

   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.

3. Maximum Observed Plasma Concentration (Cmax) of Gepotidacin for Part 1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

   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.

4. Cmax of Gepotidacin for Part 2 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both.]

   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.

5. Total Amount Excreted in Urine (Ae Total), Part 1 [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]

   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.

6. Ae Total of Gepotidacin for Part 2 [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 both treatment period 1 and 2]

   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.

7. Percentage of the Given Dose Excreted in Urine (fe%) of Gepotidacin for Part 1 [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]

   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.

8. fe% of Gepotidacin for Part 2 [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 in each of the two treatment periods]

   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.

9. Renal Clearance (CLr) of Gepotidacin for Part 1 [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]

   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.

10. CLr of Gepotidacin for Part 2 [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 in each of the two treatment periods]

    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.

11. AUC (t0-t1) of Gepotidacin for Part 2 [Dialysate fluid were to be collected on Day 1 after dosing (Period 1 only) at pre-dose from 0 to 4 hours]

    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..

12. Dialysis Clearance (CLD) of Gepotidacin for Part 2 [Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1]

    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.

13. Fraction (%) of the Dose Removed by Hemodialysis From 0 to 4 Hours After the Start of Hemodialysis (Frem%[0-4]) of Gepotidacin for Part 2 [Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1]

    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)

Secondary Outcome Measures

1. Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1 [Up to 16 Days]

   Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific timepoints during the study. No formal analysis of group comparison was planned for dialysate PK parameters

2. Number of Participants With Abnormal 12-lead ECG Readings for Part 2 [Up to 23 Days]

   Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific time points during the study. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). NA indicates data was not available

3. Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1 [Baseline and up to 16 Days]

   Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Baseline was defined as the latest pre-dose assessment. Change from Baseline, was defined as post Baseline values minus the values at Baseline.

4. Change From Baseline in Vitals- SBP and DBP, Part 2 [Baseline and up to 23 Days]

   Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

5. Change From Baseline in Vitals- Pulse Rate, Part 1 [Baseline and up to 16 Days]

   Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment

6. Change From Baseline in Vitals- Pulse Rate, Part 2 [Baseline and Up to 23 Days]

   Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

7. Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1 [Up to 16 Days]

   An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.

8. Number of Participants With Any AEs and Any SAEs for Part 2 [Up to 23 Days]

   An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.

9. Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1 [Up to 17 Days]

   The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported.

10. Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2 [Up to 24 Days]

    The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported.

11. Number of Participants With Abnormal Physical Examination Results for Part 1 [Up to 16 Days]

    Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected.

12. Number of Participants With Abnormal Physical Examination Results for Part 2 [Up to 23 Days]

    Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected.

13. AUC (0-t) of Gepotidacin for Part 1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

    Blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported.

14. AUC (0-t) of Gepotidacin for Part 2 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.]

    Serial blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported.

15. Systemic Clearance (CL) of Gepotidacin for Part 1 [At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose during the single treatment period.]

    Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf).

16. CL of Gepotidacin for Part 2 [At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose in each of the two treatment periods]

    Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf).

17. Terminal Elimination Rate Constant (lambda_z) of Gepotidacin for Part 1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

    Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour.

18. Lambda_z of Gepotidacin for Part 2 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both]

    Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour.

19. Terminal Phase Half-life (t1/2) of Gepotidacin for Part 1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

    Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.

20. t1/2 of Gepotidacin for Part 2 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.]

    Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.

21. Time to Maximum Plasma Concentration (Tmax) of Gepotidacin for Part1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

    Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

22. Tmax of Gepotidacin for Part 2 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.]

    Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

23. Volume of Distribution at Steady State of Parent Drug (Vss) of Gepotidacin for Part 1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

    Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

24. Vss of Gepotidacin for Part 2 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.]

    Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

25. Volume of Distribution of the Terminal Phase (Vz) of Gepotidacin for Part 1 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.]

    Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant.

26. Vz of Gepotidacin for Part 2 [Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.]

    Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant.

27. Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal [At Pre-dose, 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]

    Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 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 for participant's with normal renal function.

28. Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe [at pre-dose (0.0), 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 36, and 36 to 48 hours post-dose during the single treatment period]

    Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

29. Ae(t1-t2) of Gepotidacin for Part 2 [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 both treatment period 1 and 2]

    Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 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 for participant's with normal renal function. NA indicates data is not available due to insufficient participants.Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

30. Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2 [Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1Dialysate fluid were collected at 1, 2, 3, and 4 hours post-dose in Period 1 only]

    Arem is defined as the total amount of drug removed using the hemodialysis method at different timepoints namely Arem (0-1), measured the amount of drug removed by hemodialysis from time 0 to 1 hour after the start of hemodialysis; Arem (1-2), measured the amount of drug removed by hemodialysis from time 1 to 2 hours after the start of hemodialysis; Arem(2-3) ), measured the amount of drug removed by hemodialysis from time 2 to 3 hour, Arem (3-4), measured the amount of drug removed by hemodialysis from hemodialysis from time 3 to 4 hours after the start of hemodialysis (or to the end of dialysis if <4 hours). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age: Male or female subject between 18 and 80 years of age, inclusive.

• Healthy subject must be in clinically stable health as determined by the investigator based on medical history, clinical laboratory results (serum chemistry, hematology, urinalysis, and serology), vital sign measurements, 12 lead ECG results, and physical examination findings. Subject with renal impairment must have clinical laboratory values consistent with their disease and are approved by the investigator.

• Subject with renal impairment (mild, moderate, severe, or subjects with ESRD) may be taking medications, which in the opinion of the investigator, are believed to be therapeutic but do not affect study drug absorption, distribution, metabolism, or excretion. These medications must be stable doses taken for at least 7 days before the first dose of study drug.

• Subject with normal renal function or renal impairment (estimated Glomerular Filtration Rate [eGFR] corresponding to the calculated eGFR [the estimated eGFR may be rounded to the nearest integer]) at Screening.

• Subjects with ESRD on hemodialysis should be on hemodialysis for at least 3 months before Screening and is able to tolerate a hemodialysis treatment lasting 3 to 4 hours with blood flow rates of >200 milliliter (mL)/minute (min).

• Alanine aminotransferase (ALT) and bilirubin <1.5 × upper limit of normal (ULN; isolated bilirubin >1.5 × ULN is acceptable, if bilirubin is fractionated and direct bilirubin <35%).

• Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 18.5 and 40 kg/square meter (m^2), inclusive.

• Male or Female. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies:

Nonreproductive potential defined as:

• Premenopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, or Documented bilateral oophorectomy

• Postmenopausal defined as 12 months of continuous spontaneous amenorrhea (in questionable cases a blood sample will be obtained to test for simultaneous follicle-stimulating hormone) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.

Reproductive potential and agrees to follow 1 of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential requirements from 30 days prior to the first dose until completion of the Follow-up Visit.

For subjects with indeterminate pregnancy test results or a persistently low human chorionic gonadotropin results, nonpregnancy status must be documented by other means (subjects with ESRD only).

• Capable of giving signed informed consent as described in protocol, which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Exclusion Criteria:

• Subject has a clinically significant abnormality in past medical history or at the Screening physical examination (excluding renal insufficiency and other related stable medical conditions within the renally impaired population of subjects [e.g., hypertension, diabetes, or anemia, which should be stable for at least 3 months before the first dose of study drug]) that in the investigator's opinion may place the subject at risk or interfere with outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, neurologic, gastrointestinal (GI), respiratory, hematologic, or immunologic disease.

Subject has any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug, or any other condition that may place the subject at risk, in the opinion of the investigator.

• Subject has a functioning renal transplant.

• Subject with renal impairment has a systolic blood pressure outside the range of 90 to 200 millimeter of mercury (mm Hg), a diastolic blood pressure outside the range of 45 to 110 mm Hg, or a heart rate outside the range of 40 to 120 beats per minute (bpm).

• Subject with renal impairment has a hemoglobin value <9 grams (g)/decilitre (dL).

• Female subject has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic.

• Use of a systemic antibiotic within 30 days of Screening

• Within 2 months before Screening, either a confirmed history of Clostridium difficile diarrhoea infection or a past positive Clostridium difficile toxin test.

• Subject has a history of drug and/or alcohol abuse within 6 months before Screening, as determined by the investigator, or subject has a positive drug screen at Screening or upon admission to the clinic. For subjects with renal impairment, a positive drug screen result related to the use of prescription medications is allowed per investigator review and approval, and tetrahydrocannabinol use is allowed per investigator review and approval.

• History of sensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) medical monitor, contraindicates their participation.

• History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain IV cannula patency).

• Subject has used medications known to affect the elimination of serum creatinine (e.g., trimethoprim or cimetidine) or competitors of renal tubular secretion (e.g., probenecid) within 30 days before dosing.

• Subjects cannot use any over-the-counter, or prescription medication (except for hormonal contraceptives and/or acetaminophen), vitamin supplement, or herbal medication within 7 days (or 5 half-lives, whichever is longer) before dosing and during the study within 7 days before dosing and during the study.

• Subjects with normal renal function have a presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study treatment. A subject with renal impairment with stable hepatitis C who has normal liver function test results is allowed with investigator approval.

• A positive test for human immunodeficiency virus antibody.

• Subject has clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at Screening or Day -1 (and Day 7 for Group F only), other than those associated with underlying renal conditions or other stable medical conditions consistent with the disease process.

• Subject with normal renal function has a baseline corrected QT interval using the Fridericia formula (QTcF) of >450 milliseconds (msec) and subject with renal impairment has a baseline QTcF of >480 msec.

• Donation of blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

• Previous exposure to gepotidacin within 12 months prior to the first dosing day.

• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).

• Subject is unable to comply with all study procedures, in the opinion of the investigator.

• The subject should not participate in the study, in the opinion of the investigator or Sponsor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Miami	Florida	United States	33136
2	GSK Investigational Site	Orlando	Florida	United States	32809
3	GSK Investigational Site	Minneapolis	Minnesota	United States	55404

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Mar 1, 2016
• Statistical Analysis Plan - Sep 2, 2016

More Information

Publications

• Hossain M, Tiffany C, Raychaudhuri A, Nguyen D, Tai G, Alcorn H Jr, Preston RA, Marbury T, Dumont E. Pharmacokinetics of Gepotidacin in Renal Impairment. Clin Pharmacol Drug Dev. 2020 Jul;9(5):560-572. doi: 10.1002/cpdd.807. Epub 2020 May 19.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02729038
• Other Study ID Numbers: 116849
• First Posted: Apr 6, 2016
• Last Update Posted: Jul 21, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Normal Renal Function; end stage renal disease (ESRD); Pharmacokinetics; Gepotidacin; Renal Impairment
• Additional relevant MeSH terms: Bacterial Infections; Renal Insufficiency

Study Results

Participant Flow

Recruitment Details	A 2-part study, conducted in participant's with varying degree of renal impairment (RI) which enrolled 32 participants, wherein, 24 participants were enrolled in Part 1 and 8 participants in Part 2. The study was conducted, at 3 centers in United States of America from 29 June 2016 to 20 June 2017.
Pre-assignment Detail	A total of 43 participants were screened of which 8 were screen-failures and 32 were enrolled in the study and 3 participants were reserve participants and were no longer required in the study .

Arm/Group Title	Normal, Part 1	Moderate	Severe/ESRD Not on Hemodialysis, Part 1	ESRD on Hemodialysis, Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated creatinine clearance (Clcr) >= 90 milliliter per minute), in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in this period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (Period 1) and gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Period Title: Part 1 (Up to 44 Days)
STARTED	8	8	8	0
COMPLETED	8	8	8	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1 (Up to 44 Days)
STARTED	0	0	0	8
COMPLETED	0	0	0	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1	ESRD on Hemodialysis, Part 2	Total
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in this period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (Period 1) and gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).	Total of all reporting groups
Overall Participants	8	8	8	8	32
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.5 (10.78)	72.0 (7.05)	61.4 (12.49)	51.8 (7.09)	61.6 (2.72)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	1 12.5%	4 50%	1 12.5%	9 28.1%
Male	5 62.5%	7 87.5%	4 50%	7 87.5%	23 71.9%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	1 12.5%	0 0%	0 0%	1 3.1%
Black or African American	1 12.5%	1 12.5%	2 25%	8 100%	12 37.5%
White: White/Caucasian/European	7 87.5%	6 75%	5 62.5%	0 0%	18 56.3%
Multiple: African American/African/White	0 0%	0 0%	1 12.5%	0 0%	1 3.1%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration Time Curve (AUC) From Hour 0 to Infinity (AUC[0-inf]) of Gepotidacin for Part 1
Description	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.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

PK Parameter Population.

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Nanogram*hour per milliliter]	14838 (20.7)	22367 (17.0)	28545 (21.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Moderate, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	1.507
	Confidence Interval	(2-Sided) 90%; 0.902 to 2.519
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf) for participants with normal renal function Vs participants with moderate renal function has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Severe/ESRD Not on Hemodialysis, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	1.924
	Confidence Interval	(2-Sided) 90%; 1.151 to 3.215
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf) for participants with normal renal function Vs participants with Severe/ESRD not on hemodialysis

2. Primary Outcome

Title	AUC (0-inf) of Gepotidacin for Part 2
Description	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.
Time Frame	Pre-dose, 0.25 hours, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.

Outcome Measure Data

Analysis Population Description

PK Parameter Population.

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Nanogram*hour per milliliter]	14838 (20.7)	35239 (95.0)	60461 (140.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Moderate, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	2.375
	Confidence Interval	(2-Sided) 90%; 1.421 to 3.969
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf) for participants with normal renal function Vs ESRD on hemodialysis (before hemodialysis)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Severe/ESRD Not on Hemodialysis, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	4.075
	Confidence Interval	(2-Sided) 90%; 2.438 to 6.810
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf) for participants with normal renal function Vs ESRD on hemodialysis (after hemodialysis)

3. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Gepotidacin for Part 1
Description	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.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

PK Parameter Population.

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]	4498 (16.3)	5306 (16.0)	7084 (23.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Moderate, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	1.179
	Confidence Interval	(2-Sided) 90%; 0.467 to 2.977
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax for participants with normal renal function Vs participants with moderate renal function has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Severe/ESRD Not on Hemodialysis, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	1.575
	Confidence Interval	(2-Sided) 90%; 0.624 to 3.975
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax for participants with normal renal function Vs .participants with Severe/ESRD not on hemodialysis

4. Primary Outcome

Title	Cmax of Gepotidacin for Part 2
Description	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.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]	4498 (16.3)	10123 (216.3)	26839 (797.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Moderate, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	2.250
	Confidence Interval	(2-Sided) 90%; 0.891 to 5.681
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax for participants with normal renal function Vs ESRD on hemodialysis (before hemodialysis)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Severe/ESRD Not on Hemodialysis, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	5.966
	Confidence Interval	(2-Sided) 90%; 2.363 to 15.062
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax for participants with normal renal function Vs ESRD on hemodialysis (after hemodialysis)

5. Primary Outcome

Title	Total Amount Excreted in Urine (Ae Total), Part 1
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Population.

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [milligram.]	280.49 (15.2)	165.86 (39.4)	59.40 (68.3)

6. Primary Outcome

Title	Ae Total of Gepotidacin for Part 2
Description	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.
Time Frame	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 both treatment period 1 and 2

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	3	3
Geometric Mean (Geometric Coefficient of Variation) [milligram]	280.49 (15.2)	7.87 (96.4)	10.87 (64.7)

7. Primary Outcome

Title	Percentage of the Given Dose Excreted in Urine (fe%) of Gepotidacin for Part 1
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Percentage of gepotidacin]	37.40 (15.2)	22.11 (39.4)	7.92 (68.3)

8. Primary Outcome

Title	fe% of Gepotidacin for Part 2
Description	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.
Time Frame	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 in each of the two treatment periods

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	3	3
Geometric Mean (Geometric Coefficient of Variation) [Percentage of gepotidacin]	37.40 (15.2)	1.05 (96.4)	1.45 (64.7)

9. Primary Outcome

Title	Renal Clearance (CLr) of Gepotidacin for Part 1
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour]	19.24 (18.8)	7.58 (44.3)	2.13 (84.3)

10. Primary Outcome

Title	CLr of Gepotidacin for Part 2
Description	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.
Time Frame	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 in each of the two treatment periods

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	3	3
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour]	19.24 (18.8)	0.29 (101.7)	0.10 (277.5)

11. Primary Outcome

Title	AUC (t0-t1) of Gepotidacin for Part 2
Description	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..
Time Frame	Dialysate fluid were to be collected on Day 1 after dosing (Period 1 only) at pre-dose from 0 to 4 hours

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	0	8	0
Geometric Mean (Geometric Coefficient of Variation) [Nanogram*hour per milliliter]	1062 (36.3)

12. Primary Outcome

Title	Dialysis Clearance (CLD) of Gepotidacin for Part 2
Description	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.
Time Frame	Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ESRD on Hemodialysis (Before Hemodialysis), Part 2
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour]	6.63 (15.8)

13. Primary Outcome

Title	Fraction (%) of the Dose Removed by Hemodialysis From 0 to 4 Hours After the Start of Hemodialysis (Frem%[0-4]) of Gepotidacin for Part 2
Description	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)
Time Frame	Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	ESRD on Hemodialysis (Before Hemodialysis), Part 2
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [Percentage of gepotidacin removed]	5.89 (26.2)

14. Secondary Outcome

Title	Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Readings for Part 1
Description	Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific timepoints during the study. No formal analysis of group comparison was planned for dialysate PK parameters
Time Frame	Up to 16 Days

Outcome Measure Data

Analysis Population Description

The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 post dose safety assessment.

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Baseline, Abnormal, NCS	3 37.5%	6 75%	7 87.5%
Baseline, Abnormal, CS	0 0%	0 0%	0 0%
Day 1 - 1.5 hour, Abnormal, NCS	5 62.5%	6 75%	6 75%
Day 1- 1.5 hour, Abnormal, CS	0 0%	0 0%	0 0%
Day 1- 2 hour, Abnormal, NCS	3 37.5%	6 75%	6 75%
Day 1- 2 hour, Abnormal, CS	0 0%	0 0%	0 0%
Day 1 - 4 hour, Abnormal, NCS	2 25%	6 75%	7 87.5%
Day 1- 4 hour, Abnormal CS	0 0%	0 0%	0 0%
Day 1 - 8 hour, Abnormal NCS	2 25%	6 75%	6 75%
Day 1 - 8 hour, Abnormal, CS	0 0%	0 0%	0 0%
Day 1 - 12 hour, Abnormal NCS	2 25%	6 75%	7 87.5%
Day 1 - 12 hour, Abnormal, CS	0 0%	0 0%	0 0%
Day 2 - 24 hour, Abnormal NCS	3 37.5%	7 87.5%	5 62.5%
Day 2 - 24 hour, Abnormal, CS	0 0%	0 0%	0 0%
Day 2 - 36 hour, Abnormal NCS	2 25%	6 75%	6 75%
Day 2 - 36 hour, Abnormal, CS	0 0%	0 0%	0 0%
Day 3 - 48 hour, Abnormal NCS	2 25%	6 75%	5 62.5%
Day3 - 48 hour, Abnormal, CS	0 0%	0 0%	0 0%
Follow-up, Abnormal NCS	3 37.5%	5 62.5%	5 62.5%
Follow-up, Abnormal CS	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With Abnormal 12-lead ECG Readings for Part 2
Description	Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and corrected Q to T interval (QTc). The data for abnormal ECG recordings not clinically significant (NCS) and clinically significant (CS), have been reported at specific time points during the study. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). NA indicates data was not available
Time Frame	Up to 23 Days

Outcome Measure Data

Analysis Population Description

Participants

Arm/Group Title	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8
Day 1- Baseline, Abnormal CS (n=8,8)	0 0%	0 0%
Day 1 - Baseline, Abnormal NCS (n=8,8)	6 75%	7 87.5%
Day 1- 2 hour, Abnormal, NCS (n=8,0)	6 75%
Day 1- 2 hour, Abnormal, CS (n=8,0)	0 0%
Day 1 - 4 hour, Abnormal, NCS (n=8,0)	7 87.5%
Day 1- 4 hour, Abnormal CS (n=8,0)	0 0%
Day 1 - 8 hour, Abnormal NCS (n=8,0)	7 87.5%
Day 1 - 8 hour, Abnormal, CS (n=8,0)	0 0%
Day 1 - 12 hour, Abnormal NCS (n=8,0)	6 75%
Day 1 - 12 hour, Abnormal, CS (n=8,0)	0 0%
Day 2 - 24 hour, Abnormal NCS (n=8,0)	7 87.5%
Day 2 - 24 hour, Abnormal, CS (n=8,0)	0 0%
Day 2 - 36 hour, Abnormal NCS (n=8,0)	8 100%
Day 2 - 36 hour, Abnormal, CS (n=8,0)	0 0%
Day 3 - 48 hour, Abnormal NCS (n=8,0)	7 87.5%
Day3 - 48 hour, Abnormal, CS (n=8,0)	0 0%
Day 8- 2 hour, Abnormal, NCS (n=0,8)	8 100%
Day 8- 2 hour, Abnormal, CS (n=0,8)	0 0%
Day 8 - 4 hour, Abnormal, NCS (n=0,8)	8 100%
Day 8- 4 hour, Abnormal CS (n=0,8)	0 0%
Day 8 - 8 hour, Abnormal NCS (n=0,8)	7 87.5%
Day 8 - 8 hour, Abnormal, CS (n=0,8)	0 0%
Day 8 - 12 hour, Abnormal NCS (n=0,8)	8 100%
Day 8 - 12 hour, Abnormal, CS (n=0,8)	0 0%
Day 9- 24 hour, Abnormal, NCS (n=0,8)	6 75%
Day 9- 24 hour, Abnormal, CS (n=0,8)	0 0%
Day 9 - 36 hour, Abnormal, NCS (n=0,8)	8 100%
Day 9- 36 hour, Abnormal CS (n=0,8)	0 0%
Day 10 - 48 hour, Abnormal NCS (n=0,8)	7 87.5%
Day 10 - 48 hour, Abnormal, CS (n=0,8)	0 0%
Follow-up, Abnormal NCS (n=0,8)	6 75%
Follow-up, Abnormal CS (n=0,8)	0 0%

16. Secondary Outcome

Title	Change From Baseline in Vitals- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure, Part 1
Description	Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Baseline was defined as the latest pre-dose assessment. Change from Baseline, was defined as post Baseline values minus the values at Baseline.
Time Frame	Baseline and up to 16 Days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
SBP, Day 1- 1.5 hour,	3.1 (2.36)	6.8 (11.94)	-3.3 (13.77)
SBP, Day 1- 2 hour,	6.9 (12.54)	8.3 (13.39)	-4.4 (12.73)
SBP, Day 1 - 4 hour	-0.9 (12.15)	3.4 (5.42)	1.0 (13.03)
SBP, Day 1 - 8 hour,	1.3 (12.69)	5.9 (7.30)	6.0 (12.75)
SBP, Day 1 - 12 hour,	-3.4 (12.29)	14.1 (12.89)	4.6 (6.30)
SBP, Day 2 - 24 hour,	-1.1 (13.28)	5.3 (6.65)	-4.1 (11.46)
SBP, Day 2 - 36 hour	0.5 (3.74)	14.4 (13.02)	-0.4 (9.12)
SBP, Day 3 - 48 hour	-1.0 (10.72)	7.8 (9.10)	-6.0 (18.18)
SBP, Follow-up	0.8 (3.28)	8.3 (13.06)	-4.8 (18.16)
DBP, Day 1- 1.5 hour	0.1 (3.91)	-1.3 (3.92)	-3.5 (7.19)
DBP, Day 1- 2 hour,	5.8 (7.15)	1.3 (3.99)	0.4 (4.07)
DBP, Day 1 - 4 hour	3.0 (5.50)	-2.4 (8.14)	1.5 (4.99)
DBP, Day 1 - 8 hour	4.9 (6.06)	-4.3 (10.55)	-2.4 (6.95)
DBP, Day 1 - 12 hour	2.9 (6.36)	-0.5 (9.61)	-3.6 (4.66)
DBP, Day 2 - 24 hour	2.3 (5.50)	1.0 (5.55)	-2.3 (4.17)
DBP, Day 2 - 36 hour	3.1 (8.22)	-0.8 (13.07)	-3.5 (3.96)
DBP, Day 3 - 48 hour	5.0 (7.69)	0.6 (6.48)	-5.3 (5.87)
DBP, Follow-up	2.6 (5.48)	0.5 (11.60)	-1.8 (6.58)

17. Secondary Outcome

Title	Change From Baseline in Vitals- SBP and DBP, Part 2
Description	Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to 23 Days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	ESRD on Hemodialysis
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in this period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (Period 1) and gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8
SBP, Day 1- 2 hour, (n=8)	-0.5 (14.91)
SBP, Day 1 - 4 hour (n=8)	8.6 (16.66)
SBP, Day 1 - 8 hour, (n=8)	-0.6 (23.93)
SBP, Day 1 - 12 hour, (n=8)	-4.8 (17.68)
SBP, Day 2 - 24 hour, (n=8)	1.4 (9.69)
SBP, Day 2 - 36 hour (n=8)	3.9 (10.33)
SBP, Day 3 - 48 hour, (n=8)	6.5 (5.53)
SBP, Day 8-2 hour (n=8)	-2.0 (8.16)
SBP, Day 8-4 hour (n=8)	-4.4 (7.46)
SBP, Day 8-8 hour (n=8)	-14.8 (14.50)
SBP, Day 8-12 hour (n=6)	-8.3 (7.92)
SBP, Day 9-24 hour (n=8)	5.9 (23.94)
SBP, Day 9-36 hour (n=8)	2.3 (20.11)
SBP, Day 10-48 hour (n=8)	12.6 (19.72)
SBP, Follow-up, (n=8)	0.5 (11.86)
DBP, Day 1- 2 hour, (n=8)	4.3 (11.31)
DBP, Day 1 - 4 hour, (n=8)	3.6 (9.83)
DBP, Day 1 - 8 hour, (n=8)	-1.5 (11.70)
DBP, Day 1 - 12 hour (n=8)	-2.3 (9.54)
DBP, Day 2 - 24 hour (n=8)	4.6 (9.68)
DBP, Day 2 - 36 hour,(n=8)	3.3 (6.11)
DBP, Day 3 - 48 hour (n=7)	3.0 (10.10)
DBP, Day 8-2 hour, (n=8)	-2.1 (10.49)
DBP, Day 8-4 hour , (n=8)	-2.5 (9.41)
DBP, Day 8- 8 hour,(n=8)	-6.9 (8.48)
DBP, Day 8-12 hour, (n=8)	-9.5 (10.03)
DBP, Day 9-24 hour, (n=8)	6.4 (9.41)
DBP, Day 9-36 hour (n=8)	2.6 (13.41)
DBP, Day 10-48 hour (n=8)	5.9 (11.74)
DBP, Follow-up (n=8)	2.3 (6.34)

18. Secondary Outcome

Title	Change From Baseline in Vitals- Pulse Rate, Part 1
Description	Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment
Time Frame	Baseline and up to 16 Days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Pulse rate, Day 1- 1.5 hour	0.1 (9.28)	1.6 (4.21)	3.5 (4.41)
Pulse rate, Day 1- 2 hour	1.8 (7.13)	4.1 (3.23)	4.1 (5.03)
Pulse rate, Day 1 - 4 hour	0.1 (6.49)	0.4 (8.14)	2.0 (5.63)
Pulse rate, Day 1 - 8 hour	-1.0 (13.40)	1.8 (7.50)	0.8 (4.46)
Pulse rate, Day 1 - 12 hour	-0.1 (12.31)	3.4 (4.78)	3.4 (1.92)
Pulse rate, Day 2 - 24 hour	1.0 (13.06)	-0.8 (7.85)	-2.3 (5.55)
Pulse rate, Day 2 - 36 hour	1.6 (9.56)	-0.5 (5.37)	0.6 (5.24)
Pulse rate, Day 3 - 48 hour	-1.4 (10.76)	-0.1 (7.88)	-1.8 (7.34)
Pulse rate, Follow-up	-0.6 (10.34)	0.6 (8.45)	0.0 (7.43)

19. Secondary Outcome

Title	Change From Baseline in Vitals- Pulse Rate, Part 2
Description	Vital signs were measured in semi-supine position after 5 minutes of rest. The data for change from Baseline values for pulse rate was reported. Change from Baseline, was defined as post Baseline values minus the values at Baseline. Baseline was defined as the latest pre-dose assessment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Up to 23 Days

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	ESRD on Hemodialysis
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in this period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (Period 1) and gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8
Pulse rate, Day 1- 2 hour, (n=8)	0.4 (8.78)
Pulse rate, Day 1 - 4 hour, (n=8)	3.4 (9.09)
Pulse rate, Day 1 - 8 hour, (n=8)	4.4 (9.46)
Pulse rate, Day 1 - 12 hour, (n=7)	4.4 (10.21)
Pulse rate, Day 2 - 24 hour, (n=8)	2.5 (7.11)
Pulse rate, Day 2 - 36 hour, (n=8)	6.1 (9.96)
Pulse rate, Day 3 - 48 hour, (n=7)	3.6 (5.88)
Pulse rate, Day, 8-2 hour (n=8)	4.8 (10.38)
Pulse rate, Day 8-4 hour (n=7)	2.1 (5.08)
Pulse rate, Day 8-8 hour ,(n=8)	3.4 (7.69)
Pulse rate, Day 8-12 hour (n=8)	4.7 (10.05)
Pulse rate, Day 9-24 hour (n=8)	4.0 (11.51)
Pulse rate, Day9-36 hour (n=8)	8.9 (16.19)
Pulse rate, Day 10-48 hour (n=8)	3.6 (11.04)
Pulse rate, Follow-up (n=8)	3.8 (10.22)

20. Secondary Outcome

Title	Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) for Part 1
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.
Time Frame	Up to 16 Days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Any SAE	0 0%	0 0%	0 0%
Any AE	0 0%	3 37.5%	4 50%

21. Secondary Outcome

Title	Number of Participants With Any AEs and Any SAEs for Part 2
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.
Time Frame	Up to 23 Days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8
Any SAE	0 0%	0 0%
Any AE	4 50%	3 37.5%

22. Secondary Outcome

Title	Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 1
Description	The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported.
Time Frame	Up to 17 Days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Serum or plasma creatinine, Grade 3 or higher	0 0%	0 0%	5 62.5%
Serum glucose, Grade 3 or higher	0 0%	0 0%	1 12.5%

23. Secondary Outcome

Title	Number of Participants With Clinical Laboratory Test Results for Grade 3 or Higher for Part 2
Description	The adverse events reported by the participants were classified as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 as life-threatening. The data for clinical laboratory findings with values of Grade 3 or higher, have been reported.
Time Frame	Up to 24 Days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8
Serum or plasma creatinine, Grade 3 or higher	8 100%	0 0%
Serum glucose, Grade 3 or higher	2 25%	0 0%

24. Secondary Outcome

Title	Number of Participants With Abnormal Physical Examination Results for Part 1
Description	Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected.
Time Frame	Up to 16 Days

Outcome Measure Data

Analysis Population Description

Safety Population. This data was not collected.

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	0	0	0

25. Secondary Outcome

Title	Number of Participants With Abnormal Physical Examination Results for Part 2
Description	Physical exam were to be performed by a qualified individual. A complete physical examination included, at a minimum, an assessment of the cardiovascular, respiratory, GI, and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This data was not collected.
Time Frame	Up to 23 Days

Outcome Measure Data

Analysis Population Description

Safety Population: This data was not collected.

Arm/Group Title	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	0	0

26. Secondary Outcome

Title	AUC (0-t) of Gepotidacin for Part 1
Description	Blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Nanogram*hour per milliliter]	14582 (20.8)	21883 (17.1)	27886 (21.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Severe/ESRD Not on Hemodialysis, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	1.501
	Confidence Interval	(2-Sided) 90%; 0.894 to 2.520
	Parameter Dispersion	Type: Value:
	Estimation Comments	Normal Vs Moderate

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Severe/ESRD Not on Hemodialysis, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	1.912
	Confidence Interval	(2-Sided) 90%; 1.139 to 3.212
	Parameter Dispersion	Type: Value:
	Estimation Comments	Normal Vs Severe/ESRD not on hemodialysis

27. Secondary Outcome

Title	AUC (0-t) of Gepotidacin for Part 2
Description	Serial blood samples were collected at specified time-points for PK analysis. The data for Area under the concentration-time curve from time 0 (predose) to time of last quantifiable concentration for gepotidacin were reported.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Nanogram*hour per milliliter]	14582 (20.8)	34633 (95.8)	59311 (143.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Moderate, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	2.375
	Confidence Interval	(2-Sided) 90%; 1.414 to 3.989
	Parameter Dispersion	Type: Value:
	Estimation Comments	Normal Vs ESRD on hemodialysis (before hemodialysis)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal, Part 1, Severe/ESRD Not on Hemodialysis, Part 1
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric LS means
	Estimated Value	4.068
	Confidence Interval	(2-Sided) 90%; 2.422 to 6.831
	Parameter Dispersion	Type: Value:
	Estimation Comments	Normal Vs ESRD on hemodialysis (after hemodialysis)

28. Secondary Outcome

Title	Systemic Clearance (CL) of Gepotidacin for Part 1
Description	Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf).
Time Frame	At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose during the single treatment period.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour]	50.55 (20.7)	33.53 (17.0)	26.27 (21.4)

29. Secondary Outcome

Title	CL of Gepotidacin for Part 2
Description	Serial blood samples were collected at specified time-points for PK analysis. Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-inf).
Time Frame	At pre-dose and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose in each of the two treatment periods

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour]	50.55 (20.7)	21.28 (95.0)	12.40 (140.5)

30. Secondary Outcome

Title	Terminal Elimination Rate Constant (lambda_z) of Gepotidacin for Part 1
Description	Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Per hour]	0.06027 (11.9)	0.06369 (16.1)	0.06266 (13.4)

31. Secondary Outcome

Title	Lambda_z of Gepotidacin for Part 2
Description	Serial blood samples were collected at specified time-points for PK analysis. It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on during treatment period 1 and 2 both

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Per hour]	0.06027 (11.9)	0.07338 (8.4)	0.06428 (16.4)

32. Secondary Outcome

Title	Terminal Phase Half-life (t1/2) of Gepotidacin for Part 1
Description	Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Median (Full Range) [hours]	11.663	11.421	11.246

33. Secondary Outcome

Title	t1/2 of Gepotidacin for Part 2
Description	Serial blood samples were collected at specified time-points for PK analysis. t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Median (Full Range) [hours]	11.663	9.455	11.121

34. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) of Gepotidacin for Part1
Description	Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Mean (Full Range) [hours]	2.000	2.000	2.000

35. Secondary Outcome

Title	Tmax of Gepotidacin for Part 2
Description	Serial blood samples were collected at specified time-points for PK analysis. Tmax was defined as the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Median (Full Range) [hours]	2.000	2.000	1.575

36. Secondary Outcome

Title	Volume of Distribution at Steady State of Parent Drug (Vss) of Gepotidacin for Part 1
Description	Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter]	255 (21.7)	223 (14.8)	181 (23.5)

37. Secondary Outcome

Title	Vss of Gepotidacin for Part 2
Description	Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter]	255 (21.7)	114 (335.6)	49 (938.8)

38. Secondary Outcome

Title	Volume of Distribution of the Terminal Phase (Vz) of Gepotidacin for Part 1
Description	Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter]	839 (25.3)	527 (29.1)	419 (27.0)

39. Secondary Outcome

Title	Vz of Gepotidacin for Part 2
Description	Serial blood samples were collected at specified time-points for PK analysis. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz is the apparent volume of distribution at terminal phase. Volume of distribution of the terminal phase was calculated as total administered dose of gepotidacin divided by AUC (0-inf) multiplied by the rate constant.
Time Frame	Pre-dose, 0.25 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose during treatment period 1 and 2 both.

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter]	839 (25.3)	290 (90.8)	193 (161.3)

40. Secondary Outcome

Title	Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Normal
Description	Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 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 for participant's with normal renal function.
Time Frame	At Pre-dose, 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

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8
Ae(0-2)	135.53 (21.0)
Ae (2-4)	59.95 (56.7)
Ae (4-6)	19.90 (18.4)
Ae (6-8)	19.47 (70.5)
Ae (8-12)	9.11 (86.9)
Ae(12-24)	12.30 (55.3)
Ae(24-36)	5.38 (52.1)
Ae(36-48)	3.00 (42.8)

41. Secondary Outcome

Title	Cumulative Amount of Drug Excreted in Urine From Time t1 to t2 (Ae[t1-t2]) of Gepotidacin for Part 1, for Moderate and Severe
Description	Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	at pre-dose (0.0), 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 36, and 36 to 48 hours post-dose during the single treatment period

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Moderate, Part 1	Severe/ESRD Not on Hemodialysis, Part 1
Arm/Group Description	The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.
Measure Participants	8	8
Ae (0-6) (n=8, 8)	119.79 (50.0)	39.54 (94.9)
Ae (6-12) (n=8, 8)	21.67 (30.7)	8.26 (44.8)
Ae (12-24) (n=8, 8)	12.81 (40.8)	4.42 (160.0)
Ae(24-36 (n=8, 8)	5.25 (25.4)	2.89 (29.8)
Ae(36-48) (n=8,7)	2.66 (50.3)	1.17 (71.0)

42. Secondary Outcome

Title	Ae(t1-t2) of Gepotidacin for Part 2
Description	Ae (t1-t2), measure the amount of drug excreted in urine in a time intervals for predose, 0 to 6, 6 to 12, 12 to 24, or 24 to 36, and 36 to 48 hours after dosing for participant's with renal impairment; and predose, 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 for participant's with normal renal function. NA indicates data is not available due to insufficient participants.Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	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 both treatment period 1 and 2

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Normal, Part 1	ESRD on Hemodialysis (Before Hemodialysis), Part 2	ESRD on Hemodialysis (After Hemodialysis), Part 2
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
Measure Participants	8	3	3
Ae (0-8)(n=0,3,3)	5.56 (123.4)	8.12 (73.8)
Ae (8-12) (n=8,3,3)	9.11 (86.9)	0.72 (32.1)	1.16 (31.5)
Ae (12-24) (n=8,3, 3)	12.30 (55.3)	0.81 (147.5)	1.31 (52.5)
Ae (24-36) (n=8,2,1)	5.38 (52.1)	0.45 (154.4)	0.75 (NA)
Ae (36-48) (n=8,2,0)	3.00 (42.8)	0.14 (133.2)

43. Secondary Outcome

Title	Total Amount of Unchanged Amount of Drug Removed by Hemodialysis (Arem) From Time 0 to 1 Hour After the Start of Hemodialysis (Arem[0-1]), Arem (1-2), Arem (2-3), Arem (3-4) for Part 2
Description	Arem is defined as the total amount of drug removed using the hemodialysis method at different timepoints namely Arem (0-1), measured the amount of drug removed by hemodialysis from time 0 to 1 hour after the start of hemodialysis; Arem (1-2), measured the amount of drug removed by hemodialysis from time 1 to 2 hours after the start of hemodialysis; Arem(2-3) ), measured the amount of drug removed by hemodialysis from time 2 to 3 hour, Arem (3-4), measured the amount of drug removed by hemodialysis from hemodialysis from time 3 to 4 hours after the start of hemodialysis (or to the end of dialysis if <4 hours). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Pre-dose, 0-1 hours, 1-2 hours, 2-3 hours and 3-4 hours post-dose on Day 1 in Period 1Dialysate fluid were collected at 1, 2, 3, and 4 hours post-dose in Period 1 only

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	ESRD on Hemodialysis (Before Hemodialysis), Part 2
Arm/Group Description	The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).
Measure Participants	8
Arem (0-1), (n=8)	18.22 (27.7)
Arem (1-2), (n=8)	12.42 (34.8)
Arem (2-3), (n=8)	8.93 (32.5)
Arem (3-4), (n=6)	5.35 (36.6)

Adverse Events

Time Frame	AEs and SAEs were collected from the start of study treatment upto 94 days
Adverse Event Reporting Description	AEs and SAEs were collected in Safety Population.
Arm/Group Title	Normal, Part 1		Moderate, Part 1		Severe/ESRD Not on Hemodialysis, Part 1		ESRD on Hemodialysis (Before Hemodialysis)		ESRD on Hemodialysis (After Hemodialysis)
Arm/Group Description	The eligible participants, with normal renal function (participants with estimated glomerular filtration rate (eGFR) >= 90 milliliter per minute per 1.73 meter^2 or estimated Clcr >= 90 milliliter per minute, in this arm received a single dose of gepotidacin 750 milligrams, administered as 2-hour intravenous infusion on Day 1.		The eligible participants, with moderate renal function (participants with eGFR in the range of 30 to 59 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.		The eligible participants, with severe renal impairment and participants with ESRD not on hemodialysis renal function (participants with eGFR < 30 milliliter per minute per 1.73 meter^2), in this arm received a single dose of gepotidacin at 750 milligrams, administered as 2-hour intravenous infusion on Day 1.		The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 1 on Day 1 and treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour infusion starting approximately 2 hours before the initiation of the last hemodialysis session of the week (treatment period 1).		The participants in this arm, in the part 2 of the study participated in 2 treatment periods. The dosing in each period was separated by a wash-out period of 7-days. These participants, during treatment period 2 on Day 8, received a single dose of study drug gepotidacin 750 milligram, administered as a 2-hour intravenous infusion starting within 2 hours after completion of the last hemodialysis session of the week (treatment period 2).
All Cause Mortality
	Normal, Part 1		Moderate, Part 1		Severe/ESRD Not on Hemodialysis, Part 1		ESRD on Hemodialysis (Before Hemodialysis)		ESRD on Hemodialysis (After Hemodialysis)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Normal, Part 1		Moderate, Part 1		Severe/ESRD Not on Hemodialysis, Part 1		ESRD on Hemodialysis (Before Hemodialysis)		ESRD on Hemodialysis (After Hemodialysis)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Normal, Part 1		Moderate, Part 1		Severe/ESRD Not on Hemodialysis, Part 1		ESRD on Hemodialysis (Before Hemodialysis)		ESRD on Hemodialysis (After Hemodialysis)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		4/8 (50%)		4/8 (50%)		4/8 (50%)		3/8 (37.5%)
Gastrointestinal disorders
Abdominal pain	0/8 (0%)		2/8 (25%)		2/8 (25%)		0/8 (0%)		0/8 (0%)
Diarrhoea	0/8 (0%)		1/8 (12.5%)		2/8 (25%)		4/8 (50%)		0/8 (0%)
Abdominal discomfort	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Faeces soft	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Nausea	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)
Flatulence	0/8 (0%)		0/8 (0%)		0/8 (0%)		2/8 (25%)		0/8 (0%)
Dyspepsia	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
General disorders
Infusion site erythema	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)
Suprapubic pain	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Infections and infestations
Lower respiratory tract infection	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Metabolism and nutrition disorders
Hyperglycaemia	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Hypoglycaemia	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Nervous system disorders
Dizziness postural	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Headache	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		1/8 (12.5%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Oropharyngeal discomfort	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

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Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.