Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability and Plasma PK of a Single Oral Dose of Zoliflodacin in Healthy Male and Female Volunteers (NCT NCT03404167)

NCT ID: NCT03404167

Last Updated: 2019-03-18

Results Overview

Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 8 participants
• Primary outcome timeframe: From Day 1 to Day 4
• Results posted on: 2019-03-18

Participant Flow

The trial was performed at a commercial phase 1 unit. Recruitment opened on February 2, 2018 and all eight participants were consented and screened for meeting eligibility criteria prior to enrollment and dosing on Feb 23, 2018.

This was an open-label, non-randomized single-dose oral treatment of eligible participants followed by follow up to eight days after dosing.

Participant milestones

Measure	Zoliflodacin 4 g (2 sachets of 2 g) of zoliflodacin orally in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Safety, Tolerability and Plasma PK of a Single Oral Dose of Zoliflodacin in Healthy Male and Female Volunteers

Baseline characteristics by cohort

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	26.0 years STANDARD_DEVIATION 3.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants
Body Mass Index	25.50 kg/m2 STANDARD_DEVIATION 1.59 • n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to Day 4

Population: The analysis population consists of all eight participants.

Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Maximum Observed Concentration (Cmax) of Zoliflodacin	20863 ng/mL Standard Deviation 7129

PRIMARY outcome

Timeframe: From Day 1 to Day 4

Population: The analysis population consists of all eight participants.

Tmax was defined as the time at which the maximum concentration (Cmax) occurs in plasma computed from concentrations that were measured using a validated HPLC-MS/MS method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Time of Maximum Observed Concentration (Tmax) of Zoliflodacin	4 hour Standard Deviation 3

PRIMARY outcome

Timeframe: From Day 1 to Day 4

Population: The analysis population consists of all eight participants.

AUC(0-8) was defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large. AUC(0-8) and was calculated by adding AUC(0-last) to an extrapolated value equal to the last measured concentration greater than the lower limit of quantification of the bioanalytical assay divided by the terminal phase elimination rate constant (Ke) computed from concentrations that were measured using a validated HPLC-MS/MS method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin	226750 h x ng/mL Standard Deviation 85336

PRIMARY outcome

Timeframe: From Day 1 to Day 4

Population: The analysis population consists of all eight participants.

AUC(0-last) was defined as the area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration computed from concentrations that were measured using a validated HPLC-MS/MS method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin	226500 h x ng/mL Standard Deviation 85340

PRIMARY outcome

Timeframe: From Day 1 to Day 4

Population: The analysis population consists of all eight participants.

Apparent volume of distribution during terminal phase (Vz/F) after non-intravenous administration was calculated as (CL/F)/ Ke computed from concentrations that were measured using a validated HPLC-MS/MS method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Apparent Volume of Distribution (Vz/F) of Zoliflodacin	183.6 Liter Standard Deviation 58.8

PRIMARY outcome

Timeframe: Day 1 to Day 4

Population: The analysis population consists of all eight participants.

Apparent oral clearance (CL/F) computed as Dose/Area under the curve (AUC) from time zero to infinity (0-8) computed from concentrations that were measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Apparent Oral Clearance (CL/F) of Zoliflodacin	19.9 L/h Standard Deviation 7.0

PRIMARY outcome

Timeframe: From Day 1 to Day 4

Population: The analysis population consists of all eight participants.

The terminal phase elimination rate constant (Ke) was defined as the first-order rate constant describing the rate of decrease of drug concentration in the terminal phase (defined as the terminal region of the PK curve where drug concentration follows first-order elimination kinetics) computed from concentrations that were measured using a validated HPLC-MS/MS method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Elimination Rate Constant (Ke) of Zoliflodacin	0.108 1/hour Standard Deviation 0.011

PRIMARY outcome

Timeframe: From Day 1 to Day 4

Population: The analysis population consists of all eight participants.

The apparent terminal elimination half-life (t1/2) was defined as the time required for the drug concentration to decrease by a factor of one-half in the terminal phase computed from concentrations that were measured using a validated HPLC-MS/MS method.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Terminal Elimination Half-life (t1/2) of Zoliflodacin	6.5 hour Standard Deviation 0.6

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Days -1 and 4

Change from baseline calculated by subtracting the Day -1 (baseline) hematology measurement from the Day 4 hematology measurement. Hematology parameters included white blood cell count, differential (absolute counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils), and platelet count.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for White Blood Cells With Differentials and Platelets Leukocytes	-0.659 10^9/L Standard Deviation 1.668
Changes From Baseline for White Blood Cells With Differentials and Platelets Neutrophils	-0.118 10^9/L Standard Deviation 0.950
Changes From Baseline for White Blood Cells With Differentials and Platelets Lymphocytes	-0.465 10^9/L Standard Deviation 0.689
Changes From Baseline for White Blood Cells With Differentials and Platelets Monocytes	-0.036 10^9/L Standard Deviation 0.075
Changes From Baseline for White Blood Cells With Differentials and Platelets Eosinophils	-0.035 10^9/L Standard Deviation 0.096
Changes From Baseline for White Blood Cells With Differentials and Platelets Basophils	-0.008 10^9/L Standard Deviation 0.019
Changes From Baseline for White Blood Cells With Differentials and Platelets Platelets	-7.1 10^9/L Standard Deviation 21.9

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Days -1 and 4

Change from baseline calculated by subtracting the Day -1 (baseline) hematocrit measurement from the Day 4 hematocrit measurement.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline Hematocrit	1.36 percentage Standard Deviation 1.68

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Days -1 and 4

Change from baseline calculated by subtracting the Day -1 (baseline) hemoglobin measurement from the Day 4 hemoglobin measurement.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline Hemoglobin	0.46 g/dL Standard Deviation 0.66

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Days -1 and 4

Change from baseline calculated by subtracting the Day -1 (baseline) red blood cell count measurement from the Day 4 red blood cell count measurement.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline Red Blood Cell Count	0.150 10^12/L Standard Deviation 0.201

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Days -1 and 4

Change from baseline calculated by subtracting the Day -1 (baseline) albumin or total protein measurement from the Day 4 albumin or total protein measurement.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Albumin and Total Protein Albumin	0.02 g/dL Standard Deviation 0.23
Changes From Baseline for Albumin and Total Protein Total Protein	0.11 g/dL Standard Deviation 0.29

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Days -1 and 4

Change from baseline calculated by subtracting the Day -1 (baseline) AP, ALT, or AST measurement from the Day 4 AP, ALT, or AST measurement.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Change From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) Alkaline Phosphatase	-3.1 U/L Standard Deviation 7.2
Change From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) Alanine Aminotransferase	1.5 U/L Standard Deviation 4.3
Change From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) Aspartate Aminotransferase	-0.8 U/L Standard Deviation 2.7

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Days -1 and 4

Change from baseline calculated by subtracting the Day -1 (baseline) serum chemistry measurement from the Day 4 serum chemistry measurement. Serum chemistry tests for this outcome measure included BUN, creatinine, fasting glucose, magnesium, total bilirubin, and direct bilirubin.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin BUN	-3.0 mg/dL Standard Deviation 2.1
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin Creatinine	0.05 mg/dL Standard Deviation 0.08
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin Glucose (fasting)	-2.6 mg/dL Standard Deviation 3.2
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin Magnesium	-0.01 mg/dL Standard Deviation 0.08
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin Total Bilirubin	0.03 mg/dL Standard Deviation 0.31
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin Direct Bilirubin	-0.01 mg/dL Standard Deviation 0.06

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had safety labs collected on Day -1 and Day 4

Change from baseline calculated by subtracting the Day -1 (baseline) serum chemistry measurement from the Day 4 serum chemistry measurement. Serum chemistry tests for this outcome measure included sodium, potassium, chloride, and bicarbonate.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate Sodium	-1.1 mmol/L Standard Deviation 1.7
Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate Potassium	-0.24 mmol/L Standard Deviation 0.36
Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate Chloride	-3.6 mmol/L Standard Deviation 0.9
Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate Bicarbonate	0.5 mmol/L Standard Deviation 1.2

SECONDARY outcome

Timeframe: From Day -1 through Day 8

Population: Any participants who received study product and had vital signs collected on Day -1 and at least one time point post dose.

Change from baseline in systolic blood pressure calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, and 4 h after dosing, and on Day 2, Day 3, Day 4, and Day 8. Vital signs were measured after supine for at least 10 minutes.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Blood Pressure - Systolic 1 Hour	1.1 mmHg Standard Deviation 3.9
Changes From Baseline for Blood Pressure - Systolic 2 Hour	0 mmHg Standard Deviation 5.9
Changes From Baseline for Blood Pressure - Systolic 4 Hour	-3.9 mmHg Standard Deviation 6.0
Changes From Baseline for Blood Pressure - Systolic Day 2	-1.1 mmHg Standard Deviation 5.6
Changes From Baseline for Blood Pressure - Systolic Day 3	-3.6 mmHg Standard Deviation 7.4
Changes From Baseline for Blood Pressure - Systolic Day 4	0.5 mmHg Standard Deviation 6.5
Changes From Baseline for Blood Pressure - Systolic Day 8	2.4 mmHg Standard Deviation 11.4

SECONDARY outcome

Timeframe: From Day -1 through Day 8

Population: Any participants who received study product and had vital signs collected on Day -1 and at least one time point post dose.

Change from baseline in diastolic blood pressure calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, and 4 h after dosing, and on Day 2, Day 3, Day 4, and Day 8. Vital signs were measured after supine for at least 10 minutes.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Blood Pressure - Diastolic 1 Hour	0.1 mmHg Standard Deviation 5.5
Changes From Baseline for Blood Pressure - Diastolic 2 Hour	-5.3 mmHg Standard Deviation 6.1
Changes From Baseline for Blood Pressure - Diastolic 4 Hour	-4.5 mmHg Standard Deviation 6.3
Changes From Baseline for Blood Pressure - Diastolic Day 2	-2.8 mmHg Standard Deviation 7.5
Changes From Baseline for Blood Pressure - Diastolic Day 3	-4.1 mmHg Standard Deviation 6.5
Changes From Baseline for Blood Pressure - Diastolic Day 4	0.0 mmHg Standard Deviation 6.3
Changes From Baseline for Blood Pressure - Diastolic Day 8	-1.0 mmHg Standard Deviation 10.7

SECONDARY outcome

Timeframe: From Day -1 through Day 8

Population: Any participants who received study product and had vital signs collected on Day -1 and at least one time point post dose.

Change from baseline in temperature calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, and 4 h after dosing, and on Day 2, Day 3, Day 4, and Day 8. Vital signs were measured after supine for at least 10 minutes.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in Oral Temperature 1 Hour	-0.04 Degress C Standard Deviation 0.29
Changes From Baseline in Oral Temperature 2 Hour	0.03 Degress C Standard Deviation 0.17
Changes From Baseline in Oral Temperature 4 Hour	0.01 Degress C Standard Deviation 0.24
Changes From Baseline in Oral Temperature Day 2	-0.06 Degress C Standard Deviation 0.17
Changes From Baseline in Oral Temperature Day 3	-0.09 Degress C Standard Deviation 0.16
Changes From Baseline in Oral Temperature Day 4	0.06 Degress C Standard Deviation 0.21
Changes From Baseline in Oral Temperature Day 8	-0.04 Degress C Standard Deviation 0.23

SECONDARY outcome

Timeframe: From Day -1 through Day 8

Population: Any participants who received study product and had vital signs collected on Day -1 and at least one time point post dose.

Change from baseline in pulse rate calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, and 4 h after dosing, and on Day 2, Day 3, Day 4, and Day 8. Vital signs were measured after supine for at least 10 minutes.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in Pulse Rate 1 Hour	-3.8 Beats per minute Standard Deviation 11.7
Changes From Baseline in Pulse Rate 2 Hour	-0.4 Beats per minute Standard Deviation 14.0
Changes From Baseline in Pulse Rate 4 Hour	-3.5 Beats per minute Standard Deviation 12.6
Changes From Baseline in Pulse Rate Day 2	-4.3 Beats per minute Standard Deviation 12.8
Changes From Baseline in Pulse Rate Day 3	-1.8 Beats per minute Standard Deviation 8.7
Changes From Baseline in Pulse Rate Day 4	-1.9 Beats per minute Standard Deviation 13.3
Changes From Baseline in Pulse Rate Day 8	1.9 Beats per minute Standard Deviation 14.0

SECONDARY outcome

Timeframe: From Day -1 through Day 8

Population: Any participants who received study product and had vital signs collected on Day -1 and at least one time point post dose.

Change from baseline in respiratory rate calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, and 4 h after dosing, and on Day 2, Day 3, Day 4, and Day 8. Vital signs were measured after supine for at least 10 minutes.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Respiratory Rate 1 Hour	0.3 Breaths per minute Standard Deviation 1.7
Changes From Baseline for Respiratory Rate 2 Hour	1.0 Breaths per minute Standard Deviation 2.1
Changes From Baseline for Respiratory Rate 4 Hour	0.8 Breaths per minute Standard Deviation 2.4
Changes From Baseline for Respiratory Rate Day 2	0.8 Breaths per minute Standard Deviation 1.0
Changes From Baseline for Respiratory Rate Day 3	0.5 Breaths per minute Standard Deviation 0.9
Changes From Baseline for Respiratory Rate Day 4	0.5 Breaths per minute Standard Deviation 1.4
Changes From Baseline for Respiratory Rate Day 8	0.5 Breaths per minute Standard Deviation 1.8

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had an ECG collected on Day -1 and at least one time point post dose.

Change from baseline in ECG PR Interval calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, and 72 h after dosing.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex) 1 Hour	4.0 msec Standard Deviation 8.6
Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex) 2 Hour	2.3 msec Standard Deviation 6.6
Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex) 4 Hour	1.5 msec Standard Deviation 7.9
Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex) 72 Hour	6.9 msec Standard Deviation 7.7

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had an ECG collected on Day -1 and at least one time point post dose.

Change from baseline in ECG QRS Duration calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, and 72 h after dosing.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave) 1 Hour	-0.3 msec Standard Deviation 3.3
Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave) 2 Hour	0.5 msec Standard Deviation 2.7
Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave) 4 Hour	-0.1 msec Standard Deviation 2.7
Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave) 72 Hour	1.0 msec Standard Deviation 3.9

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had an ECG collected on Day -1 and at least one time point post dose.

Change from baseline in ECG QTcF Interval calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, and 72 h after dosing.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula) 1 Hour	1.8 msec Standard Deviation 13.6
Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula) 2 Hour	6.8 msec Standard Deviation 13.2
Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula) 4 Hour	4.0 msec Standard Deviation 11.6
Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula) 72 Hour	-2.6 msec Standard Deviation 11.2

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had an ECG collected on Day -1 and at least one time point post dose.

Change from baseline in ECG QT Interval calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, and 72 h after dosing.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave) 1 Hour	-1.1 msec Standard Deviation 13.8
Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave) 2 Hour	4.6 msec Standard Deviation 15.6
Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave) 4 Hour	3.6 msec Standard Deviation 10.8
Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave) 72 Hour	-6.3 msec Standard Deviation 8.8

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had an ECG collected on Day -1 and at least one time point post dose.

Change from baseline in ECG RR Interval calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, and 72 h after dosing.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in ECG: RR Interval (Interval From the Peak of the R Wave of a QRS Complex to the Peak of the R Wave of the Next QRS Complex) 1 Hour	-23.3 msec Standard Deviation 120.9
Changes From Baseline in ECG: RR Interval (Interval From the Peak of the R Wave of a QRS Complex to the Peak of the R Wave of the Next QRS Complex) 2 Hour	-20.3 msec Standard Deviation 122.3
Changes From Baseline in ECG: RR Interval (Interval From the Peak of the R Wave of a QRS Complex to the Peak of the R Wave of the Next QRS Complex) 4 Hour	-7.0 msec Standard Deviation 64.5
Changes From Baseline in ECG: RR Interval (Interval From the Peak of the R Wave of a QRS Complex to the Peak of the R Wave of the Next QRS Complex) 72 Hour	-30.1 msec Standard Deviation 77.3

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had an ECG collected on Day -1 and at least one time point post dose.

Change from baseline in ECG Ventricular Rate calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, and 72 h after dosing.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline in ECG: Ventricular Rate 1 Hour	1.4 beats per minute Standard Deviation 8.0
Changes From Baseline in ECG: Ventricular Rate 2 Hour	0.9 beats per minute Standard Deviation 6.4
Changes From Baseline in ECG: Ventricular Rate 4 Hour	0.0 beats per minute Standard Deviation 3.6
Changes From Baseline in ECG: Ventricular Rate 72 Hour	1.8 beats per minute Standard Deviation 4.9

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had urine collected on Day -1 and Day 4.

Urine for the clinical laboratory test was collected on Day -1 and Day 4. The results for occult blood were reported in categorical results. The possibilities were negative, trace, 1+, 2+, and 3+.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Occult Blood Via Dipstick	0 participants

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had urine collected on Day -1 and Day 4.

Urine for the clinical laboratory test was collected on Day -1 and Day 4. The results for glucose were reported in categorical results. The possibilities were negative, trace, 1+, 2+, and 3+.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Glucose Via Dipstick	0 Participants

SECONDARY outcome

Timeframe: From Day -1 through Day 4

Population: Any participants who received study product and had urine collected on Day -1 and Day 4.

Urine for the clinical laboratory test was collected on Day -1 and Day 4. The results for protein were reported in categorical results. The possibilities were negative, trace, 1+, 2+, and 3+.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Changes From Baseline for Protein Via Dipstick	0 Participants

SECONDARY outcome

Timeframe: From study product administration (Day 1) to Day 8

Population: Any participants who received study product

Adverse events are defined as any untoward medical occurrence regardless of its causal relationship to the study treatment.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Occurrence of Unsolicited Treatment-emergent Adverse Events	8 Participants

SECONDARY outcome

Timeframe: From study product administration (Day 1) to Day 8

Population: Any participants who received study product.

Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.

Outcome measures

Measure	Zoliflodacin n=8 Participants 4 g (2 sachets of 2 g) of zoliflodacin administered orally to eight participants in the morning of Day 1 after 8 hours of fasting AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Occurrence of Treatment-emergent Serious Adverse Events	0 Participants

Adverse Events

Zoliflodacin

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Zoliflodacin n=8 participants at risk 4 g (2 sachets of 2 g) of zoliflodacin orally in the morning of Day 1 after 8 hours of fasting, n=8 AZD0914: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Gastrointestinal disorders DIARRHOEA	12.5% 1/8 • Number of events 1 • Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8. Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 or early termination whichever came first.
Gastrointestinal disorders ABDOMINAL PAIN	12.5% 1/8 • Number of events 1 • Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8. Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 or early termination whichever came first.
Investigations ELECTROCARDIOGRAM QT PROLONGED	75.0% 6/8 • Number of events 6 • Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8. Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 or early termination whichever came first.
Investigations HEART RATE DECREASED	50.0% 4/8 • Number of events 4 • Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8. Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 or early termination whichever came first.
Investigations NEUTROPHIL COUNT DECREASED	12.5% 1/8 • Number of events 1 • Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8. Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 or early termination whichever came first.
Investigations WHITE BLOOD CELL COUNT DECREASED	12.5% 1/8 • Number of events 1 • Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8. Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 or early termination whichever came first.
Skin and subcutaneous tissue disorders DERMATITIS CONTACT	12.5% 1/8 • Number of events 1 • Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8. Treatment emergent adverse events were defined as new events post-dose, or worsening of existing conditions post-dose. The adverse events were captured by changes in laboratory values, vital signs, ECGs and unsolicited adverse events immediately post dose to Day 8 or early termination whichever came first.

Additional Information

George A. Saviolakis, MD, PhD, Medical Director

DynPort Vaccine Company LLC, a GDIT Company

Phone: 1-240-651-8116

Email: George.Saviolakis@gdit.com

Results disclosure agreements

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

Restriction type: LTE60