Infections, Bacterial
Conditions
Keywords
Child-Pugh classification, Open label, Hepatic Impairment, Gepotidacin
Brief summary
This is a two-part study which will evaluate the PK, safety, and tolerability of a single 1500 milligram (mg) oral dose of gepotidacin in subjects with normal hepatic function and in subjects with mild, moderate, and severe hepatic impairment. In Part 1, subjects with moderate hepatic impairment and subjects with normal hepatic function will be enrolled. Matching subjects with normal hepatic function in Part 1 (Group D), will be enrolled following the completion of all Day 3 assessments of the respective matched, hepatically impaired subject. In Part 2, subjects with mild (optional) and severe hepatic impairment and subjects with normal hepatic function will be enrolled concurrently based on the PK, safety, and tolerability data of Part 1. Subjects with mild hepatic impairment, may be studied if there is a significant difference in PK between subjects with moderate hepatic impairment and subjects with normal hepatic function. Subjects with severe hepatic impairment, will be studied in Part 2, provided that, the PK objectives are achieved in Part 1. A totals of 48 subjects, are planned to be enrolled in the study. The study duration is approximately of 44 days from Screening to Follow-up visit. The results from this study will enable the development of appropriate dosing recommendations in subjects with impaired hepatic function.
Interventions
DRUGGepotidacin
It is an immediate-release tablet (1500 mg (2 x 750 mg), containing gepotidacin (free base) an inactive formulation excipients.
Sponsors
Biomedical Advanced Research and Development Authority
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
There will be no masking, as this is an open-label study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must be 18 to 80 years of age inclusive, at the time of signing the informed consent. * Healthy subjects 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. * Hepatically impaired subjects must have chronic (\>6 months), stable (no acute episodes of illness within the previous 1 month prior to screening due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology. Subjects must also remain stable throughout the Screening period. * Hepatically impaired subjects, will be classified, using the Child-Pugh classification system. Subjects must have, a Child-Pugh score, of 5 to 6 (mild hepatic impairment), 7 to 9 (moderate hepatic impairment), or 10 to 15 (severe hepatic impairment), with known medical history of liver disease (with or without a known history of alcohol abuse), and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, computed tomography scan, magnetic resonance imaging, or ultrasonography) associated with unambiguous medical history. If imaging study, or biopsy is not available, then the subject should have one of the following: Physical findings such as hepatomegaly, ascites, palmar erythema, spider angiomata, abdominal venous collaterals, gynecomastia, or other physical manifestations of hepatic disease Or Laboratory findings: ALT or AST elevation (\> upper limit of normal \[ULN\]), alkaline phosphatase, or total bilirubin, or international normalized ratio (INR) elevation (\>ULN) or an albumin value that is below the lower limit of normal laboratory reference range. * Subjects with hepatic impairment may be taking medications, which in the opinion of the investigator, are believed to be therapeutic, and these medications should not interfere with the conduct of the study. Subjects with hepatic impairment should be on stable regimen of chronic medications for at least 7 days prior to dosing until completion of the Follow-Up Visit. * Subjects with hepatic impairment must have platelet counts of 30,000 × 109/Liter of blood and have not had any major bleeding episodes within the past 6 months. * Body weight \>=45 kilogram (kg) and body mass index (BMI) within the range 18.5 to 40 kg/meter\^2 (inclusive). * Male subjects must agree to use contraception, as protocol from Day -1 until completion of the Follow-up Visit or, female subject will be eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applied Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance from 30 days prior to study drug administration and until completion of the Follow-up Visit. * Capable of giving signed informed consent.
Exclusion criteria
* Subject has a clinically significant abnormality in past medical history or at the Screening physical examination (excluding hepatic insufficiency and other related medical conditions within the hepatically impaired populations, which should be stable for at least 1 month before study drug administration), 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 significant cardiac, renal, neurologic, gastrointestinal, 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. * Female subject, has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic. * Subject has used a systemic antibiotic within 7 days of Screening. * Subject has a confirmed history of Clostridium (C) difficile infection or a positive C. difficile toxin test, within 2 months before Screening. * 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 hepatic impairment, and 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 GSK medical monitor, contraindicates their participation. * History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain intravenous cannula patency). * Subject has used medications known to affect the elimination of serum creatinine (example (e.g); trimethoprim or cimetidine) or competitors of renal tubular secretion (e.g., probenecid) within 30 days before dosing. * Subject must abstain from taking prescription or nonprescription drugs (including vitamins and dietary or herbal supplements), unless specified, within 7 days (or 14 days if the drug is a potential strong enzyme inducer) or 5 half-lives (whichever is longer) prior to study drug administration until completion of the Follow-Up Visit, unless, in the opinion of the investigator and Sponsor, the medication will not interfere with the study. Any exceptions (including subjects with hepatic impairment that will be on medications during the study), will be discussed with the sponsor or medical monitor on a case-by-case basis and the reasons will be documented. * Previous exposure to gepotidacin, within 12 months prior to study drug administration. * Subject has participated in a clinical trial and has received an investigational product within the following time period prior to study drug administration 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 with normal hepatic function has presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to study drug administration. Subject with hepatic impairment has evidence of recent, acute infection with hepatitis B and/or hepatitis C within preceding 6 months. Hepatically impaired subjects with chronic hepatitis B or C (duration \>6 months) will be eligible for enrolment. * A positive test for human immunodeficiency virus antibody. * Subject must be able to abstain from alcohol and limit use of nicotine and/or nicotine-containing products (up to 5 cigarettes/day is acceptable for subjects with hepatic impairment) for 24 hours before the start of dosing until after collection of the final PK sample. A positive alcohol or cotinine test is not exclusionary for subjects with hepatic impairment. * Subject has clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at Screening or Day -1, other than those associated with underlying hepatic conditions or other stable medical conditions consistent with the disease process in subjects with hepatic impairment. * Subject with normal hepatic function has a baseline corrected QT interval using the Fridericia formula (QTcF) of \>450 milliseconds (msec) and subject with hepatic impairment has a baseline QTcF of \>480 msec. * Donation of blood in excess of 500 milliliter (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. * Subject is unable to comply with all study procedures, in the opinion of the investigator. * Subject should not participate in the study, in the opinion of the investigator or Sponsor. * Subjects with a pre-existing condition (except hepatic impairment) interfering with normal gastrointestinal (GI) anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of inflammatory bowel disease should be excluded. Subjects with a history of pepticulceration or pancreatitis within the preceding 6 months of screening, should be excluded. * Subject with any previous GI surgery (except appendectomy or gall bladder removal \>3 months prior to Screening) may be enrolled in this study only if, in the opinion of the investigator and the medical monitor, it is not expected to interfere with the study procedures or to pose an additional safety risk to the subject. * Subject receiving lactulose who are medically unable to halt lactulose administration from 8 hours before dosing with study drug to 4 hours after dosing with study drug. * Subjects with clinically active severe encephalopathy (grade 3 or 4) as judged by the investigator or significant central nervous system disease (e.g., dementia or seizures) which the investigator considers will interfere with the informed consent, conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject. Subjects with a prior history of severe encephalopathy, who are currently treated for this condition will receive the appropriate score for encephalopathy. * Subjects with estimated creatinine clearance (Clcr) \<=50 mL/minute (calculated by the Cockcroft-Gault Formula). If the result calculated by Cockcroft-Gault is between 40 and 50 mL/minute, then the site may complete a 24-hour urine collection to more specifically calculate the Clcr. A Clcr value \<=50 mL/minute via 24-hour urine collection is also exclusionary. * History of gastric or esophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated with medication and/or surgical procedures. * Subjects with electrolyte imbalance whose serum sodium levels are \<=125 millimole per Liter (mmol/L); potassium levels are \<=2.5 mmol/L; or calcium levels are \<=6.1 mmol/L. * Presence of hepatopulmonary or hepatorenal syndrome. * Primary cholestatic liver diseases. * History of liver transplantation or subjects in the severe hepatic impairment group that are expecting a liver transplant during the study participation period. * Subjects with signs of active bacterial infection (including active spontaneous bacterial peritonitis). * Subjects with transjugular intrahepatic portosystemic shunt placement within the past 3 months. * Subjects with unstable cardiac function or subjects with hypertension whose blood pressure, that is not well controlled (based on the investigator's discretion). * Diabetic subjects whose diabetes that is not controlled (based on the investigator's discretion).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinity (AUC[0-inf]) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | 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. |
| Maximum Observed Concentration (Cmax) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence (Tmax) of Cmax for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
| Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
| Apparent Oral Clearance (CL/F) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
| Apparent Volume of Distribution of the Terminal Phase (Vz/F) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
| Terminal-phase Rate Constant (Lambda_z) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
| Terminal Phase Half Life (t1/2) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
| AUC(0-48) of Gepotidacin | 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 | Urine samples were collected from participants at indicated time points to evaluate AUC(0-48) PK parameter of gepotidacin. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 1.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose | 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. |
| Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | 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 | 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. |
| Change From Baseline Values in Heart Rate | 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 | 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. |
| Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Up to Day 15 | 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. |
| AUC(0-24) of Gepotidacin | Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours, 8-12 hours and 12-24 hours post dose | Urine samples were collected from participants at indicated time points to evaluate AUC(0-24) PK parameter of gepotidacin. |
| Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | Baseline and at Day 2 | 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. |
| Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein | Baseline and at Day 2 | 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. |
| Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Baseline and at Day 2 | 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. |
| Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Baseline and at Day 2 | 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. |
| Number of Participants With Toxicity Grading 3 or Higher for Hematology Parameters | Up to 15 days | Blood samples were collected to measure the number of participants with toxicity grades higher than 3 or 4 for blood neurtophils and blood platelets. |
| Number of Participants With Toxicity Grading 3 or Higher for Urinalysis Parameters | Up to 15 days | Urine samples were collected and specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones were analyzed by dipstick method. |
| Number of Participants With Abnormal Findings During Physical Examinations | Pre-dose up to 31 days prior to dosing | 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. |
| Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin | 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 | 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. |
| Percentage of the Given Dose of Drug Excreted in Urine (Fe%) | 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 | 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. |
| Renal Clearance (CLr) of Gepotidacin | 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 | Urine samples were collected from participants at indicated time points. Renal clearance for gepotidacin was calculated as Ae\_total divided by AUC (0-t). |
| AUC(0-12) of Gepotidacin | Pre-dose, 0-2 hours, 2-4 hours, 4-6 hours, 6-8 hours and 8-12 hours post dose | Urine samples were collected from participants at indicated time points to evaluate AUC(0-12) PK parameter of gepotidacin. |
| Number of Participants With Toxicity Grading 3 or Higher for Clinical Chemistry Parameters | Up to Day 15 | 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. |
| AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC [0-t]) for Plasma Gepotidacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| 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. | 8 |
| 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. | 8 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1, Up to 3 Days | Adverse Event | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Participants With Severe Hepatic Impairment | Total | Participants With Normal Hepatic Function | Participants With Moderate Hepatic Impairment |
|---|---|---|---|---|
| Age, Continuous | 58.1 Years STANDARD_DEVIATION 6.15 | 60.1 Years STANDARD_DEVIATION 6.34 | 59.8 Years STANDARD_DEVIATION 5.7 | 62.5 Years STANDARD_DEVIATION 7.19 |
| Race/Ethnicity, Customized African American/African Heritage | 0 Participants | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 7 Participants | 21 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 23 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 3 / 9 | 2 / 8 | 4 / 8 |
| serious Total, serious adverse events | 1 / 9 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinity (AUC[0-inf]) for Plasma Gepotidacin
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | 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 |
| Participants With Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinity (AUC[0-inf]) for Plasma Gepotidacin | 19505.7 Hours*nanograms per milliliter | Geometric Coefficient of Variation 42.6 |
| Participants With Severe Hepatic Impairment | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinity (AUC[0-inf]) for Plasma Gepotidacin | 25415.5 Hours*nanograms per milliliter | Geometric Coefficient of Variation 30.1 |
Primary
Maximum Observed Concentration (Cmax) for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Maximum Observed Concentration (Cmax) for Plasma Gepotidacin | 3196.8 Nanograms per milliliter | Geometric Coefficient of Variation 85 |
| Participants With Moderate Hepatic Impairment | Maximum Observed Concentration (Cmax) for Plasma Gepotidacin | 3913.7 Nanograms per milliliter | Geometric Coefficient of Variation 64.1 |
| Participants With Severe Hepatic Impairment | Maximum Observed Concentration (Cmax) for Plasma Gepotidacin | 5541.8 Nanograms per milliliter | Geometric Coefficient of Variation 42.7 |
Secondary
Apparent Oral Clearance (CL/F) for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Apparent Oral Clearance (CL/F) for Plasma Gepotidacin | 94.37 Liters per hours | Geometric Coefficient of Variation 44.1 |
| Participants With Moderate Hepatic Impairment | Apparent Oral Clearance (CL/F) for Plasma Gepotidacin | 76.90 Liters per hours | Geometric Coefficient of Variation 42.6 |
| Participants With Severe Hepatic Impairment | Apparent Oral Clearance (CL/F) for Plasma Gepotidacin | 59.02 Liters per hours | Geometric Coefficient of Variation 30.1 |
Secondary
Apparent Volume of Distribution of the Terminal Phase (Vz/F) for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Apparent Volume of Distribution of the Terminal Phase (Vz/F) for Plasma Gepotidacin | 1235.3 Liters | Geometric Coefficient of Variation 57.5 |
| Participants With Moderate Hepatic Impairment | Apparent Volume of Distribution of the Terminal Phase (Vz/F) for Plasma Gepotidacin | 944.7 Liters | Geometric Coefficient of Variation 50.3 |
| Participants With Severe Hepatic Impairment | Apparent Volume of Distribution of the Terminal Phase (Vz/F) for Plasma Gepotidacin | 699.1 Liters | Geometric Coefficient of Variation 41.7 |
Secondary
AUC(0-12) of Gepotidacin
Urine samples were collected from participants at indicated time points to evaluate AUC(0-12) PK parameter of gepotidacin.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | AUC(0-12) of Gepotidacin | 1201 Hours*micrograms per milliliter | Standard Deviation 1033.5 |
| Participants With Moderate Hepatic Impairment | AUC(0-12) of Gepotidacin | 3030 Hours*micrograms per milliliter | Standard Deviation 2245.5 |
| Participants With Severe Hepatic Impairment | AUC(0-12) of Gepotidacin | 4771 Hours*micrograms per milliliter | Standard Deviation 4678.3 |
Secondary
AUC(0-24) of Gepotidacin
Urine samples were collected from participants at indicated time points to evaluate AUC(0-24) PK parameter of gepotidacin.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | AUC(0-24) of Gepotidacin | 1269 Hours*micrograms per milliliter | Standard Deviation 1040.4 |
| Participants With Moderate Hepatic Impairment | AUC(0-24) of Gepotidacin | 2925 Hours*micrograms per milliliter | Standard Deviation 1868.3 |
| Participants With Severe Hepatic Impairment | AUC(0-24) of Gepotidacin | 5807 Hours*micrograms per milliliter | Standard Deviation 5151 |
Secondary
AUC(0-48) of Gepotidacin
Urine samples were collected from participants at indicated time points to evaluate AUC(0-48) PK parameter of gepotidacin.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | AUC(0-48) of Gepotidacin | 1394 Hours*micrograms per milliliter | Standard Deviation 1252.4 |
| Participants With Moderate Hepatic Impairment | AUC(0-48) of Gepotidacin | 3547 Hours*micrograms per milliliter | Standard Deviation 1667.9 |
| Participants With Severe Hepatic Impairment | AUC(0-48) of Gepotidacin | 5035 Hours*micrograms per milliliter | Standard Deviation 4695.6 |
Secondary
AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC [0-t]) for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | 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 |
| Participants With Moderate Hepatic Impairment | AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC [0-t]) for Plasma Gepotidacin | 19151.6 Hours*nanograms per milliliter | Geometric Coefficient of Variation 43.4 |
| Participants With Severe Hepatic Impairment | AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC [0-t]) for Plasma Gepotidacin | 25066.8 Hours*nanograms per milliliter | Geometric Coefficient of Variation 30.5 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein
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.
Time frame: Baseline and at Day 2
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein | Albumin, Day 2 | -1.3 Grams per liter | Standard Deviation 2.35 |
| Participants With Normal Hepatic Function | Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein | Protein, Day 2 | -0.9 Grams per liter | Standard Deviation 4.26 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein | Albumin, Day 2 | -0.4 Grams per liter | Standard Deviation 1.6 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein | Protein, Day 2 | 0.8 Grams per liter | Standard Deviation 2.82 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein | Albumin, Day 2 | -1.7 Grams per liter | Standard Deviation 2.8 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein | Protein, Day 2 | -3.5 Grams per liter | Standard Deviation 5.72 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK
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.
Time frame: Baseline and at Day 2
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALT, Day 2 | -2.1 International units per liter | Standard Deviation 5.9 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | AST, Day 2 | -1.5 International units per liter | Standard Deviation 4.31 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALP, Day 2 | -4.4 International units per liter | Standard Deviation 5.21 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALT, Day 2 | -0.1 International units per liter | Standard Deviation 4.19 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | CK, Day 2 | -36.4 International units per liter | Standard Deviation 35.73 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALP, Day 2 | -5.2 International units per liter | Standard Deviation 4.36 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALT, Day 2 | -3.7 International units per liter | Standard Deviation 6.59 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | CK, Day 2 | -32.3 International units per liter | Standard Deviation 79.05 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: ALT, ALP, AST and CK | AST, Day 2 | -7.8 International units per liter | Standard Deviation 10.59 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine
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.
Time frame: Baseline and at Day 2
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 2 | -0.3230 Micromoles per liter | Standard Deviation 0.7125 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Creatinine, Day 2 | 7.6245 Micromoles per liter | Standard Deviation 15.89752 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Bilirubin, Day 2 | -1.924 Micromoles per liter | Standard Deviation 4.9592 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 2 | -0.5771 Micromoles per liter | Standard Deviation 0.8906 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Bilirubin, Day 2 | -7.695 Micromoles per liter | Standard Deviation 12.6932 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 2 | -1.8525 Micromoles per liter | Standard Deviation 2.71759 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine | Creatinine, Day 2 | -0.4420 Micromoles per liter | Standard Deviation 4.83379 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea
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.
Time frame: Baseline and at Day 2
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Urea, Day 2 | 0.4909 Millimoles per liter | Standard Deviation 1.29336 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Calcium, Day 2 | -0.01623 Millimoles per liter | Standard Deviation 0.059119 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Glucose, Day 2 | 0.04855 Millimoles per liter | Standard Deviation 0.755546 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Potassium, Day 2 | 0.35 Millimoles per liter | Standard Deviation 0.307 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Sodium, Day 2 | 0.6 Millimoles per liter | Standard Deviation 2.33 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Glucose, Day 2 | -0.79563 Millimoles per liter | Standard Deviation 2.183639 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Urea, Day 2 | 0.2975 Millimoles per liter | Standard Deviation 0.57194 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Sodium, Day 2 | 0.7 Millimoles per liter | Standard Deviation 1.97 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Calcium, Day 2 | -0.05488 Millimoles per liter | Standard Deviation 0.092641 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea | Potassium, Day 2 | 0.02 Millimoles per liter | Standard Deviation 0.337 |
Secondary
Change From Baseline Values in Heart Rate
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 4 hours | -3.7 Beats per minute | Standard Deviation 8.79 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 8 hours | -1.3 Beats per minute | Standard Deviation 7.91 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 48 hours | -0.7 Beats per minute | Standard Deviation 3.94 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 2 hours | -0.8 Beats per minute | Standard Deviation 7.98 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 12 hours | 3.9 Beats per minute | Standard Deviation 12.23 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 36 hours | 3.8 Beats per minute | Standard Deviation 9.76 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 1.5 hours | 0.3 Beats per minute | Standard Deviation 7.47 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Heart Rate | 24 hours | -4.3 Beats per minute | Standard Deviation 6.78 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 1.5 hours | 0.6 Beats per minute | Standard Deviation 9.86 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 36 hours | 3.8 Beats per minute | Standard Deviation 3.2 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 48 hours | 2.8 Beats per minute | Standard Deviation 7.19 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 4 hours | 1.4 Beats per minute | Standard Deviation 4.44 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 24 hours | -1.1 Beats per minute | Standard Deviation 6.64 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 8 hours | 2.6 Beats per minute | Standard Deviation 4.9 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 12 hours | 4.8 Beats per minute | Standard Deviation 3.58 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Heart Rate | 2 hours | -0.1 Beats per minute | Standard Deviation 10.2 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 48 hours | -0.9 Beats per minute | Standard Deviation 6.56 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 2 hours | 0.8 Beats per minute | Standard Deviation 5.6 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 4 hours | 0.1 Beats per minute | Standard Deviation 6.77 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 8 hours | 1.0 Beats per minute | Standard Deviation 4.93 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 12 hours | 5.1 Beats per minute | Standard Deviation 7.26 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 24 hours | -2.0 Beats per minute | Standard Deviation 8.12 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 36 hours | 2.4 Beats per minute | Standard Deviation 9.68 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Heart Rate | 1.5 hours | -0.6 Beats per minute | Standard Deviation 6.5 |
Secondary
Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 8 hours | -7.0 Millimeters of mercury | Standard Deviation 4.8 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hours | -6.6 Millimeters of mercury | Standard Deviation 11.58 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 36 hours | 2.0 Millimeters of mercury | Standard Deviation 8.86 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 48 hours | -10.6 Millimeters of mercury | Standard Deviation 19.38 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hours | -3.4 Millimeters of mercury | Standard Deviation 12 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1.5 hours | -3.5 Millimeters of mercury | Standard Deviation 7.05 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 2 hours | -5.1 Millimeters of mercury | Standard Deviation 6.29 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 48 hours | 0.9 Millimeters of mercury | Standard Deviation 11.32 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 4 hours | -0.9 Millimeters of mercury | Standard Deviation 6.75 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1.5 hours | -6.1 Millimeters of mercury | Standard Deviation 11.86 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 36 hours | -1.3 Millimeters of mercury | Standard Deviation 5.5 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 2 hours | -7.5 Millimeters of mercury | Standard Deviation 7.82 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 8 hours | -2.9 Millimeters of mercury | Standard Deviation 5.51 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 4 hours | -3.0 Millimeters of mercury | Standard Deviation 8.85 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 8 hours | -0.5 Millimeters of mercury | Standard Deviation 8.25 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hours | -0.6 Millimeters of mercury | Standard Deviation 8 |
| Participants With Moderate Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hours | -3.1 Millimeters of mercury | Standard Deviation 6.24 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 4 hours | 3.4 Millimeters of mercury | Standard Deviation 6.19 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hours | -4.9 Millimeters of mercury | Standard Deviation 8.1 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hours | 1.9 Millimeters of mercury | Standard Deviation 7.26 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 4 hours | 0.5 Millimeters of mercury | Standard Deviation 9.61 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 36 hours | -2.6 Millimeters of mercury | Standard Deviation 12.64 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 48 hours | 0.8 Millimeters of mercury | Standard Deviation 6.18 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1.5 hours | -3.8 Millimeters of mercury | Standard Deviation 7.65 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 48 hours | -5.3 Millimeters of mercury | Standard Deviation 14.04 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 8 hours | -0.8 Millimeters of mercury | Standard Deviation 7.69 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hours | -1.9 Millimeters of mercury | Standard Deviation 12.78 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1.5 hours | 1.1 Millimeters of mercury | Standard Deviation 9.25 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hours | -1.0 Millimeters of mercury | Standard Deviation 10.68 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 2 hours | -0.1 Millimeters of mercury | Standard Deviation 11.96 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 2 hours | 2.4 Millimeters of mercury | Standard Deviation 7.17 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 8 hours | -2.9 Millimeters of mercury | Standard Deviation 6.79 |
| Participants With Severe Hepatic Impairment | Change From Baseline Values in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 36 hours | -1.1 Millimeters of mercury | Standard Deviation 6.33 |
Secondary
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Normal Hepatic Function | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) for Plasma Gepotidacin | 0.50 Hours |
| Participants With Moderate Hepatic Impairment | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) for Plasma Gepotidacin | 0.00 Hours |
| Participants With Severe Hepatic Impairment | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) for Plasma Gepotidacin | 0.00 Hours |
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
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.
Time frame: 1.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 24 hours, not clinically significant | 6 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 4 hours, clinically significant | 0 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 48 hours, clinically significant | 0 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 12 hours, clinically significant | 0 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 8 hours, not clinically significant | 3 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 36 hours, clinically significant | 0 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 12 hours, not clinically significant | 2 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 8 hours, clinically significant | 0 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 2 hours, not clinically significant | 5 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 1.5 hours, not clinically significant | 1 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 36 hours, not clinically significant | 2 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 2 hours, clinically significant | 0 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 48 hours, not clinically significant | 4 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 24 hours, clinically significant | 0 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 4 hours, not clinically significant | 6 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 1.5 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 2 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 8 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 1.5 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 2 hours, not clinically significant | 6 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 1.5 hours, not clinically significant | 6 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 4 hours, not clinically significant | 6 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 4 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 8 hours, not clinically significant | 5 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 12 hours, not clinically significant | 4 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 12 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 24 hours, not clinically significant | 5 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 24 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 36 hours, not clinically significant | 5 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 36 hours, clinically significant | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 48 hours, not clinically significant | 5 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 48 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 24 hours, not clinically significant | 5 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 2 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 48 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 24 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 2 hours, not clinically significant | 5 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 48 hours, not clinically significant | 5 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 36 hours, not clinically significant | 4 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 1.5 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 8 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 8 hours, not clinically significant | 4 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 12 hours, not clinically significant | 2 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 4 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 36 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 12 hours, clinically significant | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 4 hours, not clinically significant | 5 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 1.5 hours, not clinically significant | 3 Participants |
Secondary
Number of Participants With Abnormal Findings During Physical Examinations
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.
Time frame: Pre-dose up to 31 days prior to dosing
Population: Safety Population. This analysis was planned but data was not captured in the database.
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
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.
Time frame: Up to Day 15
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Normal Hepatic Function | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Any Non-SAE | 3 Participants |
| Participants With Normal Hepatic Function | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Any SAE | 1 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Any Non-SAE | 2 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Any SAE | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Any Non-SAE | 4 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Any SAE | 0 Participants |
Secondary
Number of Participants With Toxicity Grading 3 or Higher for Clinical Chemistry Parameters
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.
Time frame: Up to Day 15
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Normal Hepatic Function | Number of Participants With Toxicity Grading 3 or Higher for Clinical Chemistry Parameters | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Toxicity Grading 3 or Higher for Clinical Chemistry Parameters | 1 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Toxicity Grading 3 or Higher for Clinical Chemistry Parameters | 6 Participants |
Secondary
Number of Participants With Toxicity Grading 3 or Higher for Hematology Parameters
Blood samples were collected to measure the number of participants with toxicity grades higher than 3 or 4 for blood neurtophils and blood platelets.
Time frame: Up to 15 days
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Normal Hepatic Function | Number of Participants With Toxicity Grading 3 or Higher for Hematology Parameters | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Toxicity Grading 3 or Higher for Hematology Parameters | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Toxicity Grading 3 or Higher for Hematology Parameters | 2 Participants |
Secondary
Number of Participants With Toxicity Grading 3 or Higher for Urinalysis Parameters
Urine samples were collected and specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones were analyzed by dipstick method.
Time frame: Up to 15 days
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Normal Hepatic Function | Number of Participants With Toxicity Grading 3 or Higher for Urinalysis Parameters | 0 Participants |
| Participants With Moderate Hepatic Impairment | Number of Participants With Toxicity Grading 3 or Higher for Urinalysis Parameters | 0 Participants |
| Participants With Severe Hepatic Impairment | Number of Participants With Toxicity Grading 3 or Higher for Urinalysis Parameters | 0 Participants |
Secondary
Percentage of the Given Dose of Drug Excreted in Urine (Fe%)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Percentage of the Given Dose of Drug Excreted in Urine (Fe%) | 8.51 Percentage of drug | Standard Deviation 4.237 |
| Participants With Moderate Hepatic Impairment | Percentage of the Given Dose of Drug Excreted in Urine (Fe%) | 12.76 Percentage of drug | Standard Deviation 5.625 |
| Participants With Severe Hepatic Impairment | Percentage of the Given Dose of Drug Excreted in Urine (Fe%) | 21.69 Percentage of drug | Standard Deviation 8.285 |
Secondary
Renal Clearance (CLr) of Gepotidacin
Urine samples were collected from participants at indicated time points. Renal clearance for gepotidacin was calculated as Ae\_total divided by AUC (0-t).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Renal Clearance (CLr) of Gepotidacin | 8.18 Liters per hour | Standard Deviation 3.209 |
| Participants With Moderate Hepatic Impairment | Renal Clearance (CLr) of Gepotidacin | 9.45 Liters per hour | Standard Deviation 2.71 |
| Participants With Severe Hepatic Impairment | Renal Clearance (CLr) of Gepotidacin | 12.46 Liters per hour | Standard Deviation 3.911 |
Secondary
Terminal Phase Half Life (t1/2) for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Terminal Phase Half Life (t1/2) for Plasma Gepotidacin | 9.073 Hours | Geometric Coefficient of Variation 14.9 |
| Participants With Moderate Hepatic Impairment | Terminal Phase Half Life (t1/2) for Plasma Gepotidacin | 8.515 Hours | Geometric Coefficient of Variation 12.3 |
| Participants With Severe Hepatic Impairment | Terminal Phase Half Life (t1/2) for Plasma Gepotidacin | 8.210 Hours | Geometric Coefficient of Variation 15.2 |
Secondary
Terminal-phase Rate Constant (Lambda_z) for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Normal Hepatic Function | Terminal-phase Rate Constant (Lambda_z) for Plasma Gepotidacin | 0.07639 Per hour | Geometric Coefficient of Variation 14.9 |
| Participants With Moderate Hepatic Impairment | Terminal-phase Rate Constant (Lambda_z) for Plasma Gepotidacin | 0.08140 Per hour | Geometric Coefficient of Variation 12.3 |
| Participants With Severe Hepatic Impairment | Terminal-phase Rate Constant (Lambda_z) for Plasma Gepotidacin | 0.08443 Per hour | Geometric Coefficient of Variation 15.2 |
Secondary
Time to First Occurrence (Tmax) of Cmax for Plasma Gepotidacin
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Normal Hepatic Function | Time to First Occurrence (Tmax) of Cmax for Plasma Gepotidacin | 3.000 Hours |
| Participants With Moderate Hepatic Impairment | Time to First Occurrence (Tmax) of Cmax for Plasma Gepotidacin | 2.750 Hours |
| Participants With Severe Hepatic Impairment | Time to First Occurrence (Tmax) of Cmax for Plasma Gepotidacin | 2.250 Hours |
Secondary
Total Unchanged Drug (Ae_total) and Amount of Drug Excreted in Urine in a Time Intervals (Ae (t1-t2) for Gepotidacin
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.
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Normal Hepatic Function | 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 |
| Participants With Moderate Hepatic Impairment | 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 | 8.44 Milligrams | Standard Deviation 3.914 |
| Participants With Moderate Hepatic Impairment | 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 | 191.39 Milligrams | Standard Deviation 84.368 |
| Participants With Moderate Hepatic Impairment | 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 |
| Participants With Moderate Hepatic Impairment | 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 | 4.59 Milligrams | Standard Deviation 3.512 |
| Participants With Moderate Hepatic Impairment | 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 |
| Participants With Moderate Hepatic Impairment | 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 | 12.72 Milligrams | Standard Deviation 7.265 |
| Participants With Severe Hepatic Impairment | 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 | 6.04 Milligrams | Standard Deviation 2.909 |
| Participants With Severe Hepatic Impairment | 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 | 199.28 Milligrams | Standard Deviation 103.407 |
| Participants With Severe Hepatic Impairment | 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 | 112.65 Milligrams | Standard Deviation 93.439 |
| Participants With Severe Hepatic Impairment | 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 | 23.27 Milligrams | Standard Deviation 17.258 |
| Participants With Severe Hepatic Impairment | 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 | 12.78 Milligrams | Standard Deviation 6.869 |
| Participants With Severe Hepatic Impairment | 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 | 325.31 Milligrams | Standard Deviation 124.273 |