Trial Outcomes & Findings for Pharmacokinetics (PK) Study of Gepotidacin (GSK2140944) in Adult Subjects With Varying Degrees of Hepatic Impairment and in Matched Control Subjects With Normal Hepatic Function (NCT NCT03562117)

NCT ID: NCT03562117

Last Updated: 2021-04-12

Results Overview

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters. PK parameter population consist of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. This population was used in the assessment and characterization of PK parameters.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 25 participants
• Primary outcome timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose
• Results posted on: 2021-04-12

Participant Flow

This was a Phase I, non-randomized, open-label, parallel-group, multi-center, two-part study that evaluated the pharmacokinetics, safety, and tolerability of a single 1500 milligrams (mg) oral dose of gepotidacin in participants with normal hepatic function and in participants with mild, moderate, and severe hepatic impairment.

Twenty five participants were enrolled in the study. In part 1, normal hepatic function participants were matched to moderate hepatic impaired participants. In Part 2, participants with severe hepatic impairment were matched to normal hepatic function participants who participated in Part1.

Participant milestones

Measure	Participants With Normal Hepatic Function Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Part 1, Up to 3 Days STARTED	8	8	0
Part 1, Up to 3 Days COMPLETED	7	8	0
Part 1, Up to 3 Days NOT COMPLETED	1	0	0
Part 2, Up to 3 Days STARTED	8	0	8
Part 2, Up to 3 Days COMPLETED	8	0	8
Part 2, Up to 3 Days NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Participants With Normal Hepatic Function Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Part 1, Up to 3 Days Adverse Event	1	0	0

Baseline Characteristics

Pharmacokinetics (PK) Study of Gepotidacin (GSK2140944) in Adult Subjects With Varying Degrees of Hepatic Impairment and in Matched Control Subjects With Normal Hepatic Function

Baseline characteristics by cohort

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Total n=25 Participants Total of all reporting groups
Age, Continuous	59.8 Years STANDARD_DEVIATION 5.70 • n=5 Participants	62.5 Years STANDARD_DEVIATION 7.19 • n=7 Participants	58.1 Years STANDARD_DEVIATION 6.15 • n=5 Participants	60.1 Years STANDARD_DEVIATION 6.34 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	6 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters. PK parameter population consist of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. This population was used in the assessment and characterization of PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinity (AUC[0-inf]) for Plasma Gepotidacin	15894.7 Hours*nanograms per milliliter Geometric Coefficient of Variation 44.1	19505.7 Hours*nanograms per milliliter Geometric Coefficient of Variation 42.6	25415.5 Hours*nanograms per milliliter Geometric Coefficient of Variation 30.1

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Maximum Observed Concentration (Cmax) for Plasma Gepotidacin	3196.8 Nanograms per milliliter Geometric Coefficient of Variation 85.0	3913.7 Nanograms per milliliter Geometric Coefficient of Variation 64.1	5541.8 Nanograms per milliliter Geometric Coefficient of Variation 42.7

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC [0-t]) for Plasma Gepotidacin	15512.9 Hours*nanograms per milliliter Geometric Coefficient of Variation 45.8	19151.6 Hours*nanograms per milliliter Geometric Coefficient of Variation 43.4	25066.8 Hours*nanograms per milliliter Geometric Coefficient of Variation 30.5

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Time to First Occurrence (Tmax) of Cmax for Plasma Gepotidacin	3.000 Hours Interval 1.5 to 6.0	2.750 Hours Interval 2.5 to 4.0	2.250 Hours Interval 0.5 to 4.0

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) for Plasma Gepotidacin	0.50 Hours Interval 0.0 to 2.5	0.00 Hours Interval 0.0 to 1.0	0.00 Hours Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Apparent Oral Clearance (CL/F) for Plasma Gepotidacin	94.37 Liters per hours Geometric Coefficient of Variation 44.1	76.90 Liters per hours Geometric Coefficient of Variation 42.6	59.02 Liters per hours Geometric Coefficient of Variation 30.1

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Apparent Volume of Distribution of the Terminal Phase (Vz/F) for Plasma Gepotidacin	1235.3 Liters Geometric Coefficient of Variation 57.5	944.7 Liters Geometric Coefficient of Variation 50.3	699.1 Liters Geometric Coefficient of Variation 41.7

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Terminal-phase Rate Constant (Lambda_z) for Plasma Gepotidacin	0.07639 Per hour Geometric Coefficient of Variation 14.9	0.08140 Per hour Geometric Coefficient of Variation 12.3	0.08443 Per hour Geometric Coefficient of Variation 15.2

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

Population: PK Parameter Population.

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Terminal Phase Half Life (t1/2) for Plasma Gepotidacin	9.073 Hours Geometric Coefficient of Variation 14.9	8.515 Hours Geometric Coefficient of Variation 12.3	8.210 Hours Geometric Coefficient of Variation 15.2

SECONDARY outcome

Timeframe: 1.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Safety Population.

Single 12-lead ECG was obtained in a semi-supine position after 5 minutes rest using an ECG machine. Safety Population consists of all participants who received at least 1 dose of study drug and had at least one postdose safety assessment. Number of participants with abnormal-clinically significant and abnormal-not clinically significant values has been presented. Absolute QTc Interval >450 milliseconds (msec), absolute PR interval <110 msec and absolute QRS interval <75 msec was considered as clinically significant ECG findings.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 1.5 hours, not clinically significant	1 Participants	6 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 1.5 hours, clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 2 hours, not clinically significant	5 Participants	6 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 2 hours, clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 4 hours, not clinically significant	6 Participants	6 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 4 hours, clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 8 hours, not clinically significant	3 Participants	5 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 8 hours, clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 12 hours, not clinically significant	2 Participants	4 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 12 hours, clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 24 hours, not clinically significant	6 Participants	5 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 24 hours, clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 36 hours, not clinically significant	2 Participants	5 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 36 hours, clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 48 hours, not clinically significant	4 Participants	5 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings 48 hours, clinically significant	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and at 1.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Safety Population.

Vital signs were measured in a semi-supine position after 5 minutes rest. Baseline is defined as Day 1 (Pre-Dose). Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 1.5 hours	-10.4 Millimeters of mercury Standard Deviation 15.19	-6.1 Millimeters of mercury Standard Deviation 11.86	-3.8 Millimeters of mercury Standard Deviation 7.65
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 2 hours	-10.3 Millimeters of mercury Standard Deviation 10.99	-7.5 Millimeters of mercury Standard Deviation 7.82	-0.1 Millimeters of mercury Standard Deviation 11.96
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 4 hours	-6.2 Millimeters of mercury Standard Deviation 11.53	-3.0 Millimeters of mercury Standard Deviation 8.85	0.5 Millimeters of mercury Standard Deviation 9.61
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 8 hours	-10.1 Millimeters of mercury Standard Deviation 9.64	-0.5 Millimeters of mercury Standard Deviation 8.25	-2.9 Millimeters of mercury Standard Deviation 6.79
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 12 hours	-5.1 Millimeters of mercury Standard Deviation 9.43	-0.6 Millimeters of mercury Standard Deviation 8.00	-1.9 Millimeters of mercury Standard Deviation 12.78
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 24 hours	-9.8 Millimeters of mercury Standard Deviation 15.75	-6.6 Millimeters of mercury Standard Deviation 11.58	-4.9 Millimeters of mercury Standard Deviation 8.10
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 36 hours	-7.3 Millimeters of mercury Standard Deviation 13.98	2.0 Millimeters of mercury Standard Deviation 8.86	-2.6 Millimeters of mercury Standard Deviation 12.64
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, 48 hours	-6.7 Millimeters of mercury Standard Deviation 13.08	-10.6 Millimeters of mercury Standard Deviation 19.38	-5.3 Millimeters of mercury Standard Deviation 14.04
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 1.5 hours	-6.8 Millimeters of mercury Standard Deviation 8.84	-3.5 Millimeters of mercury Standard Deviation 7.05	1.1 Millimeters of mercury Standard Deviation 9.25
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 2 hours	-6.4 Millimeters of mercury Standard Deviation 6.13	-5.1 Millimeters of mercury Standard Deviation 6.29	2.4 Millimeters of mercury Standard Deviation 7.17
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 4 hours	-3.8 Millimeters of mercury Standard Deviation 7.12	-0.9 Millimeters of mercury Standard Deviation 6.75	3.4 Millimeters of mercury Standard Deviation 6.19
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 8 hours	-7.0 Millimeters of mercury Standard Deviation 4.80	-2.9 Millimeters of mercury Standard Deviation 5.51	-0.8 Millimeters of mercury Standard Deviation 7.69
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 12 hours	-5.4 Millimeters of mercury Standard Deviation 3.64	-3.1 Millimeters of mercury Standard Deviation 6.24	1.9 Millimeters of mercury Standard Deviation 7.26
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 24 hours	-8.4 Millimeters of mercury Standard Deviation 8.69	-3.4 Millimeters of mercury Standard Deviation 12.00	-1.0 Millimeters of mercury Standard Deviation 10.68
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 36 hours	-9.3 Millimeters of mercury Standard Deviation 7.26	-1.3 Millimeters of mercury Standard Deviation 5.50	-1.1 Millimeters of mercury Standard Deviation 6.33
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, 48 hours	-6.6 Millimeters of mercury Standard Deviation 8.38	0.9 Millimeters of mercury Standard Deviation 11.32	0.8 Millimeters of mercury Standard Deviation 6.18

SECONDARY outcome

Timeframe: Baseline (Day 1) and at 1.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose

Population: Safety Population.

Vital signs was measured in a semi-supine position after 5 minutes rest. Baseline is defined as Day 1 (Pre-Dose). Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Change From Baseline Values in Heart Rate 1.5 hours	0.3 Beats per minute Standard Deviation 7.47	0.6 Beats per minute Standard Deviation 9.86	-0.6 Beats per minute Standard Deviation 6.50
Change From Baseline Values in Heart Rate 2 hours	-0.8 Beats per minute Standard Deviation 7.98	-0.1 Beats per minute Standard Deviation 10.20	0.8 Beats per minute Standard Deviation 5.60
Change From Baseline Values in Heart Rate 4 hours	-3.7 Beats per minute Standard Deviation 8.79	1.4 Beats per minute Standard Deviation 4.44	0.1 Beats per minute Standard Deviation 6.77
Change From Baseline Values in Heart Rate 8 hours	-1.3 Beats per minute Standard Deviation 7.91	2.6 Beats per minute Standard Deviation 4.90	1.0 Beats per minute Standard Deviation 4.93
Change From Baseline Values in Heart Rate 12 hours	3.9 Beats per minute Standard Deviation 12.23	4.8 Beats per minute Standard Deviation 3.58	5.1 Beats per minute Standard Deviation 7.26
Change From Baseline Values in Heart Rate 24 hours	-4.3 Beats per minute Standard Deviation 6.78	-1.1 Beats per minute Standard Deviation 6.64	-2.0 Beats per minute Standard Deviation 8.12
Change From Baseline Values in Heart Rate 36 hours	3.8 Beats per minute Standard Deviation 9.76	3.8 Beats per minute Standard Deviation 3.20	2.4 Beats per minute Standard Deviation 9.68
Change From Baseline Values in Heart Rate 48 hours	-0.7 Beats per minute Standard Deviation 3.94	2.8 Beats per minute Standard Deviation 7.19	-0.9 Beats per minute Standard Deviation 6.56

SECONDARY outcome

Timeframe: Up to Day 15

Population: Safety Population.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs Any Non-SAE	3 Participants	2 Participants	4 Participants
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs Any SAE	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 15

Population: Safety Population.

Blood samples were collected to measure the number of participants with toxicity grades higher than 3 or 4, for urea, Creatine kinase (CK), creatinine, glucose, sodium, potassium, calcium, Aspartate Aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) levels, total and direct bilirubin, total protein, and albumin.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Number of Participants With Toxicity Grading 3 or Higher for Clinical Chemistry Parameters	0 Participants	1 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline and at Day 2

Population: Safety Population. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected to analyze clinical chemistry parameters including: ALT, ALP, AST and CK. Baseline is defined as Day 1 (Pre-Dose). Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=6 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK ALT, Day 2	-2.1 International units per liter Standard Deviation 5.90	-0.1 International units per liter Standard Deviation 4.19	-3.7 International units per liter Standard Deviation 6.59
Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK ALP, Day 2	-1.3 International units per liter Standard Deviation 7.98	-4.4 International units per liter Standard Deviation 5.21	-5.2 International units per liter Standard Deviation 4.36
Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK AST, Day 2	-1.8 International units per liter Standard Deviation 2.59	-1.5 International units per liter Standard Deviation 4.31	-7.8 International units per liter Standard Deviation 10.59
Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK CK, Day 2	-52.9 International units per liter Standard Deviation 57.31	-36.4 International units per liter Standard Deviation 35.73	-32.3 International units per liter Standard Deviation 79.05

SECONDARY outcome

Timeframe: Baseline and at Day 2

Population: Safety Population. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected to analyze clinical chemistry parameters including albumin and protein. Baseline is defined as Day 1 (Pre-Dose). Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=6 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein Albumin, Day 2	-1.3 Grams per liter Standard Deviation 2.35	-0.4 Grams per liter Standard Deviation 1.60	-1.7 Grams per liter Standard Deviation 2.80
Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein Protein, Day 2	-0.9 Grams per liter Standard Deviation 4.26	0.8 Grams per liter Standard Deviation 2.82	-3.5 Grams per liter Standard Deviation 5.72

SECONDARY outcome

Timeframe: Baseline and at Day 2

Population: Safety Population. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected to analyze clinical chemistry parameters including bilirubin, direct bilirubin and creatinine. Baseline is defined as Day 1 (Pre-Dose). Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=6 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine Bilirubin, Day 2	-2.470 Micromoles per liter Standard Deviation 4.6131	-1.924 Micromoles per liter Standard Deviation 4.9592	-7.695 Micromoles per liter Standard Deviation 12.6932
Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine Creatinine, Day 2	-3.2413 Micromoles per liter Standard Deviation 5.97927	7.6245 Micromoles per liter Standard Deviation 15.89752	-0.4420 Micromoles per liter Standard Deviation 4.83379
Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine Direct bilirubin, Day 2	-0.3230 Micromoles per liter Standard Deviation 0.71250	-0.5771 Micromoles per liter Standard Deviation 0.89060	-1.8525 Micromoles per liter Standard Deviation 2.71759

SECONDARY outcome

Timeframe: Baseline and at Day 2

Population: Safety Population. Only those participants with data available at the specified data points were analyzed.

Blood samples were collected to analyze clinical chemistry parameters including calcium, glucose, potassium, sodium and urea. Baseline is defined as Day 1 (Pre-Dose). Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=6 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea Calcium, Day 2	-0.00831 Millimoles per liter Standard Deviation 0.065033	-0.01623 Millimoles per liter Standard Deviation 0.059119	-0.05488 Millimoles per liter Standard Deviation 0.092641
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea Glucose, Day 2	-0.08016 Millimoles per liter Standard Deviation 0.514103	0.04855 Millimoles per liter Standard Deviation 0.755546	-0.79563 Millimoles per liter Standard Deviation 2.183639
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea Potassium, Day 2	0.01 Millimoles per liter Standard Deviation 0.481	0.35 Millimoles per liter Standard Deviation 0.307	0.02 Millimoles per liter Standard Deviation 0.337
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea Sodium, Day 2	-0.4 Millimoles per liter Standard Deviation 1.67	0.6 Millimoles per liter Standard Deviation 2.33	0.7 Millimoles per liter Standard Deviation 1.97
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea Urea, Day 2	0.1983 Millimoles per liter Standard Deviation 0.92942	0.4909 Millimoles per liter Standard Deviation 1.29336	0.2975 Millimoles per liter Standard Deviation 0.57194

SECONDARY outcome

Timeframe: Up to 15 days

Population: Safety Population.

Blood samples were collected to measure the number of participants with toxicity grades higher than 3 or 4 for blood neurtophils and blood platelets.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Number of Participants With Toxicity Grading 3 or Higher for Hematology Parameters	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 15 days

Population: Safety Population.

Urine samples were collected and specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones were analyzed by dipstick method.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Number of Participants With Toxicity Grading 3 or Higher for Urinalysis Parameters	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose up to 31 days prior to dosing

Population: Safety Population. This analysis was planned but data was not captured in the database.

A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal 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 analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours, 8-12 hours, 12-24 hours, 24-36 hours and 36-48 hours post-dose

Population: PK Parameter Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Urine samples were collected from participants at indicated time points. Ae_total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Ae (t1-t2) was the amount of drug excreted in urine in time intervals for predose, 0 to 6, 6 to 12, 12 to 24, 24 to 36, and 36 to 48 hours after dosing for participants with hepatic 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 participants with normal hepatic function. It was calculated by multiplication of the urine concentration for a time interval and the length of this time interval.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae_total, n=6, 6, 6	127.67 Milligrams Standard Deviation 63.552	191.39 Milligrams Standard Deviation 84.368	325.31 Milligrams Standard Deviation 124.273
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (0-2), n=8, 0, 0	5.82 Milligrams Standard Deviation 7.838	—	—
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (2-4), n=9, 0, 0	55.53 Milligrams Standard Deviation 55.735	—	—
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (4-6), n=9, 0, 0	28.79 Milligrams Standard Deviation 19.702	—	—
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (0-6), n=0, 7, 8	—	144.24 Milligrams Standard Deviation 104.112	199.28 Milligrams Standard Deviation 103.407
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (6-8), n=9, 0, 0	18.67 Milligrams Standard Deviation 8.371	—	—
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (6-12), n=0, 7, 8	—	60.53 Milligrams Standard Deviation 35.231	112.65 Milligrams Standard Deviation 93.439
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (8-12), n=9, 0, 0	16.21 Milligrams Standard Deviation 7.056	—	—
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (12-24), n=7, 6, 7	11.15 Milligrams Standard Deviation 6.007	12.72 Milligrams Standard Deviation 7.265	23.27 Milligrams Standard Deviation 17.258
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (24-36), n=8, 7, 7	6.62 Milligrams Standard Deviation 4.675	8.44 Milligrams Standard Deviation 3.914	12.78 Milligrams Standard Deviation 6.869
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin Ae (36-48), n=6, 8, 7	3.71 Milligrams Standard Deviation 1.845	4.59 Milligrams Standard Deviation 3.512	6.04 Milligrams Standard Deviation 2.909

SECONDARY outcome

Timeframe: Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours, 8-12 hours, 12-24 hours, 24-36 hours and 36-48 hours post-dose

Population: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Urine samples were collected from participants at indicated time points. Percentage of the given dose of drug excreted in urine was calculated as: (Ae_total divided by Dose) and multiplied by 100.

Outcome measures

Measure	Participants With Normal Hepatic Function n=6 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=6 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Percentage of the Given Dose of Drug Excreted in Urine (Fe%)	8.51 Percentage of drug Standard Deviation 4.237	12.76 Percentage of drug Standard Deviation 5.625	21.69 Percentage of drug Standard Deviation 8.285

SECONDARY outcome

Timeframe: Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours, 8-12 hours, 12-24 hours, 24-36 hours and 36-48 hours post-dose

Population: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Urine samples were collected from participants at indicated time points. Renal clearance for gepotidacin was calculated as Ae_total divided by AUC (0-t).

Outcome measures

Measure	Participants With Normal Hepatic Function n=6 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=6 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Renal Clearance (CLr) of Gepotidacin	8.18 Liters per hour Standard Deviation 3.209	9.45 Liters per hour Standard Deviation 2.710	12.46 Liters per hour Standard Deviation 3.911

SECONDARY outcome

Timeframe: Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours and 8-12 hours post dose

Population: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Urine samples were collected from participants at indicated time points to evaluate AUC(0-12) PK parameter of gepotidacin.

Outcome measures

Measure	Participants With Normal Hepatic Function n=9 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=7 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
AUC(0-12) of Gepotidacin	1201 Hours*micrograms per milliliter Standard Deviation 1033.5	3030 Hours*micrograms per milliliter Standard Deviation 2245.5	4771 Hours*micrograms per milliliter Standard Deviation 4678.3

SECONDARY outcome

Timeframe: Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours, 8-12 hours and 12-24 hours post dose

Population: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Urine samples were collected from participants at indicated time points to evaluate AUC(0-24) PK parameter of gepotidacin.

Outcome measures

Measure	Participants With Normal Hepatic Function n=7 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=6 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=7 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
AUC(0-24) of Gepotidacin	1269 Hours*micrograms per milliliter Standard Deviation 1040.4	2925 Hours*micrograms per milliliter Standard Deviation 1868.3	5807 Hours*micrograms per milliliter Standard Deviation 5151.0

SECONDARY outcome

Timeframe: Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours, 8-12 hours, 12-24 hours, 24-36 hours and 36-48 hours post dose

Population: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Urine samples were collected from participants at indicated time points to evaluate AUC(0-48) PK parameter of gepotidacin.

Outcome measures

Measure	Participants With Normal Hepatic Function n=6 Participants Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=5 Participants Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=6 Participants Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
AUC(0-48) of Gepotidacin	1394 Hours*micrograms per milliliter Standard Deviation 1252.4	3547 Hours*micrograms per milliliter Standard Deviation 1667.9	5035 Hours*micrograms per milliliter Standard Deviation 4695.6

Adverse Events

Participants With Normal Hepatic Function

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Participants With Moderate Hepatic Impairment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Participants With Severe Hepatic Impairment

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Participants With Normal Hepatic Function n=9 participants at risk Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 participants at risk Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 participants at risk Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
General disorders Death	11.1% 1/9 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	0.00% 0/8 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	0.00% 0/8 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population

Other adverse events

Measure	Participants With Normal Hepatic Function n=9 participants at risk Participants with normal hepatic function received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Moderate Hepatic Impairment n=8 participants at risk Participants with moderate hepatic function having Child-Pugh score of 7 to 9 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.	Participants With Severe Hepatic Impairment n=8 participants at risk Participants with severe hepatic function having Child-Pugh score of 10 to 15 received a single oral dose of gepotidacin 1500 mg administered as 2 × 750 mg tablets on Day 1.
Gastrointestinal disorders Diarrhoea	33.3% 3/9 • Number of events 3 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	25.0% 2/8 • Number of events 2 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	25.0% 2/8 • Number of events 2 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population
Gastrointestinal disorders Nausea	0.00% 0/9 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	0.00% 0/8 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	12.5% 1/8 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population
Nervous system disorders Headache	0.00% 0/9 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	12.5% 1/8 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	12.5% 1/8 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population
Blood and lymphatic system disorders Leukopenia	0.00% 0/9 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	0.00% 0/8 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	12.5% 1/8 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/9 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	12.5% 1/8 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	0.00% 0/8 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population
Metabolism and nutrition disorders Decreased appetite	0.00% 0/9 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	0.00% 0/8 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population	12.5% 1/8 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 15 days Non-serious AEs and SAEs were collected for Safety population

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER