CClinicalTrials.gg
Sign In
CompletedNCT03404167Updated Mar 18, 2019Results posted

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

A Phase 1 interventional study of AZD0914 in Gonorrhoea, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-03-18.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
8
Allocation
Non-randomized
Ages
18 Years to 45 Years
Sex
All
01

Study summary

The trial is to evaluate the pharmacokinetics and safety profiles of the single-dose of zoliflodacin in eight healthy male or female subjects ages 18 to 45 years inclusive. All subjects will be dosed in the morning of Day 1 in a staggered fashion with a minimum of several minutes apart. Each subject will receive a single 4g dose of zoliflodacin (2 x 2 g sachets of zoliflodacin) after at least an 8-h fast, which will continue for at least 4 h after dosing. Consumption of water will be permitted during the fasting period. Subjects will be monitored as inpatients in the Clinical Trial Unit (CTU) up to Day 4 and at the Final Visit (Day 8 ± 2). Study duration is approximately 4 weeks with subject participation duration up to 10 days (from dosing to final visit). The primary objective of this study is to evaluate the plasma PK of zoliflodacin after administration of a single 4-g oral dose under fasting conditions.

Read the detailed description

The trial will be performed as an open-label, non-randomized, single-dose design in eight healthy male or female subjects ages 18 to 45 years inclusive to evaluate the pharmacokinetics and safety profiles of the zoliflodacin formulation. All subjects will be dosed in the morning of Day 1 in a staggered fashion with a minimum of several minutes apart. Each subject will receive a single 4g dose of zoliflodacin (2 x 2 g sachets of zoliflodacin) after at least an 8-h fast, which will continue for at least 4 h after dosing. Consumption of water will be permitted during the fasting period. Subjects will be monitored as inpatients in the Clinical Trial Unit (CTU) up to Day 4 and at the Final Visit (Day 8 ± 2). Study duration is approximately 4 weeks with subject participation duration up to 10 days (from dosing to final visit). The primary objective of this study is to evaluate the plasma PK of zoliflodacin after administration of a single 4-g oral dose under fasting conditions. The secondary objective is to evaluate the safety and tolerability of a single 4-g oral dose of zoliflodacin.

02

Conditions studied

  • Gonorrhoea

Browse trials for

Keywords

  • ETX0914
  • Plasma Pharmacokinetic
  • Safety
  • Tolerability
  • Zoliflodacin
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Informed consent form (ICF) understood and signed before initiating any study procedures
  2. Healthy male or female, as assessed by the authorized site clinician (listed on FDA Form 1572)
  3. Willingness to comply with and be available for all protocol procedures including inpatient confinement for about 4 days and availability for follow-up for the duration of the trial
  4. Aged 18 to 45 years inclusive on the day of study drug dosing
  5. Body Mass Index (BMI) > / = 18.5 and \< / = 30 kg/m\^2 and weight > / = 50 kg (110 lbs.) and \< / = 100 kg (220 lbs.)

  6. In female subjects of childbearing potential, a negative serum pregnancy test at Screening Visit and on Day -1

    • Note: A woman is considered of childbearing potential unless post-menopausal (> / = 1 year without menses without other known or suspected cause and with a FSH level in the menopausal range), or surgically sterilized (hysterectomy, salpingectomy, oophorectomy or tubal ligation/occlusion)
  7. If female, not pregnant, not breast feeding, and not planning on becoming pregnant during the trial and for 30 days after study participation

  8. Females of childbearing potential and males agree to use acceptable contraception for the duration of the trial and for 30 days (females) or 90 days (males) after final study visit

    • Note: A highly effective method of birth control is defined as one with a low failure rate (i.e., less than 1 percent per year) according to the CDC criteria. These include progestin implants, intrauterine devices (IUDs), surgical (hysterectomy, salpingectomy, oophorectomy or tubal ligation/occlusion; vasectomy), or abstinence. Use of methods with higher failure rate (such as progestin injectables, combined oral hormonal contraceptives, condoms, and diaphragms) will not be acceptable when used alone, but they could be considered if used in combination with another method (e.g., a female using combined oral contraceptives if her male partner is sterile, or if she and her non-sterile male partner use a double-barrier method), after consultation with the DMID Medical Officer
  9. Male subjects must agree to refrain from sperm donation for the duration of the trial and for 90 days after Final Visit
  10. Laboratory tests are in the normal reference range with acceptable exceptions
  11. Vital signs are within the acceptable range
  12. Has adequate venous access for blood collection
  13. Urine drug screen is negative for tested substances
  14. Alcohol test (breathalyzer) is negative
  15. Willing to abstain from alcohol consumption for 2 days before Day -1 and during the trial

Exclusion criteria

Exclusion Criteria:

  1. History of a chronic medical or surgical condition that would interfere with the accurate assessment of the trial's objectives or increase the subject's risk profile

  • Note: Chronic medical conditions include: diabetes mellitus; asthma requiring use of medication in the year before screening; autoimmune disorder such as lupus erythematosus, Wegener's, rheumatoid arthritis, thyroid disease; cardiovascular disease, including coronary artery disease or cerebrovascular disease, or surgery; syncope related to cardiac arrhythmia or unexplained; chronic hypertension; malignancy except low-grade (squamous and basal cell) skin cancer thought to be cured; chronic renal, hepatic, pulmonary, or endocrine disease, myopathy, or neuropathy; gastrointestinal or biliary surgery.

    1. History of hypersensitivity or severe allergic reaction of any type to medications, bee stings, food, or environmental factors
  • Note: Severe allergic reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema 3) Active allergic symptoms to seasonal and animal allergens that require treatment 4) A marked baseline prolongation of ECG intervals, or HR \< 45 bpm or > 100 bpm on ECG measurements
  • Note: The following are considered prolonged ECG intervals: QTc/QTcF > 449 msec in males and females; PR > 209 msec; and QRS > 110 msec 5) Clinically significant abnormal ECG results
  • Note: Clinically significant abnormal ECG results include: complete left or right bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree atrioventricular (AV) block; sustained atrial or ventricular arrhythmia; two premature ventricular contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; evidence of a previous myocardial infarction (MI), left ventricular hypertrophy (LVH), or more than minor non-specific ST-T wave changes; or any condition deemed clinically significant by a study investigator 6) Abnormal renal function
  • Note: Normal renal function is defined as normal creatinine and normal estimated glomerular filtration rate (eGFR) [i.e., > 80.0 mL/min] values according to Cockroft-Gault 7) Positive serology results for HIV, HBsAg, or HCV 8) Febrile illness with temperature > 37.6°C for \< 7 days before dosing 9) Donated whole blood or blood products within 60 days before dosing, or plans to donate before Final Visit (Day 8 ± 2)
  • Note: Blood products include RBCs, WBCs, platelets, and plasma 10) Known allergic reactions to any of the study drug components present in the formulation or in its processing, as listed in the IB 11) Treatment with another investigational product within 30 days of dosing or 5 half-lives or twice the duration of the biological effect of the study drug (whichever is longer)
  • Note: Investigational products include a drug, vaccine, biologic, device or blood product 12) Active drug or alcohol use, abuse, or dependence within 12 months before Screening Visit that, in the opinion of the investigator, would interfere with adherence to study requirements 13) Use of any prescription medication within 30 days before dosing or planned use during the study period except as noted below and approved by the designated study clinician
  • Note 1: Prohibited medications include moderate or strong CYP3A4 inducers; antibiotics; injectable or oral antidiabetic drugs; anti-lipid drugs; immunosuppressive agents; immune modulators; oral corticosteroids; anti-neoplastic agents; any vaccine (licensed or investigational) except licensed influenza vaccine during the flu season, which is allowed 7 days before or after dosing

  • Note 2: Allowed medications include: oral contraceptives; H1 antihistamines; topical/ intranasal corticosteroids; nonsteroidal anti-inflammatory drugs [NSAIDS]; licensed influenza vaccine during the flu season, 7 days before or after dosing.

    1. Use of any non-prescription medication, herbal preparation, or nutritional supplement within 15 days before dosing or planned use during the study unless approved by the study clinician
  • Note: Exceptions: St. John's wart is not allowed within 30 days of dosing, vitamins and OTC medications taken for a brief period (\<48 h) for the treatment of common symptoms (such as headache, indigestion, muscle pain) may be allowed as approved by the designated study clinician 15) Intake of caffeinated beverages or food within 72 h before dosing or a history of high caffeine consumption (e.g., in the last 4 months drinking > 5 cups of coffee/day) 16) Smoking or use of tobacco or nicotine-containing products within 15 days before dosing 17) Engagement in strenuous exercise within 15 days before dosing (e.g., marathon running, long distance cycling, weight lifting) and during the study period 18) Any specific behavioral or clinical condition that in the judgment of the investigator precludes participation because it could affect compliance with study procedures or subject safety 19) Plans to enroll or is already enrolled in another clinical trial that could interfere with safety assessment of the study drug at any time during the study period
  • Note: Includes trials that have a study intervention such as a drug, biologic, or device 20) Is a study site employee or staff member who is paid entirely or partially by the OCRR/NIAID contract for the DMID-funded trial
  • Note: Site employees or staff include the PIs, sub-investigators, or staff who are supervised by the PI or sub-investigators
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
8 participants (actual)

Study arms

  • Experimental
    Zoliflodacin

    4 g (2 sachets of 2 g) of zoliflodacin orally in the morning of Day 1 after 8 hours of fasting, n=8

    Drug: AZD0914

Interventions

  • DrugAZD0914

    Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent

05

What researchers measure

Primary outcomes

  1. Maximum Observed Concentration (Cmax) of Zoliflodacin

    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.

    Time frame: From Day 1 to Day 4

  2. Time of Maximum Observed Concentration (Tmax) of Zoliflodacin

    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.

    Time frame: From Day 1 to Day 4

  3. Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin

    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.

    Time frame: From Day 1 to Day 4

  4. Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin

    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.

    Time frame: From Day 1 to Day 4

  5. Apparent Volume of Distribution (Vz/F) of Zoliflodacin

    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.

    Time frame: From Day 1 to Day 4

  6. Apparent Oral Clearance (CL/F) of Zoliflodacin

    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.

    Time frame: Day 1 to Day 4

  7. Elimination Rate Constant (Ke) of Zoliflodacin

    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.

    Time frame: From Day 1 to Day 4

  8. Terminal Elimination Half-life (t1/2) of Zoliflodacin

    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.

    Time frame: From Day 1 to Day 4

Secondary outcomes

  1. Changes From Baseline for White Blood Cells With Differentials and Platelets

    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.

    Time frame: From Day -1 through Day 4

  2. Changes From Baseline Hematocrit

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

    Time frame: From Day -1 through Day 4

  3. Changes From Baseline Hemoglobin

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

    Time frame: From Day -1 through Day 4

  4. Changes From Baseline Red Blood Cell Count

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

    Time frame: From Day -1 through Day 4

  5. Changes From Baseline for Albumin and Total Protein

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

    Time frame: From Day -1 through Day 4

  6. Change From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)

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

    Time frame: From Day -1 through Day 4

  7. Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin

    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.

    Time frame: From Day -1 through Day 4

  8. Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate

    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.

    Time frame: From Day -1 through Day 4

  9. Changes From Baseline for Blood Pressure - Systolic

    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.

    Time frame: From Day -1 through Day 8

  10. Changes From Baseline for Blood Pressure - Diastolic

    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.

    Time frame: From Day -1 through Day 8

  11. Changes From Baseline in Oral Temperature

    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.

    Time frame: From Day -1 through Day 8

  12. Changes From Baseline in Pulse Rate

    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.

    Time frame: From Day -1 through Day 8

  13. Changes From Baseline for Respiratory Rate

    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.

    Time frame: From Day -1 through Day 8

  14. Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex)

    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.

    Time frame: From Day -1 through Day 4

  15. Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave)

    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.

    Time frame: From Day -1 through Day 4

  16. Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula)

    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.

    Time frame: From Day -1 through Day 4

  17. Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave)

    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.

    Time frame: From Day -1 through Day 4

  18. 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)

    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.

    Time frame: From Day -1 through Day 4

  19. Changes From Baseline in ECG: Ventricular Rate

    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.

    Time frame: From Day -1 through Day 4

  20. Changes From Baseline for Occult Blood Via Dipstick

    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+.

    Time frame: From Day -1 through Day 4

  21. Changes From Baseline for Glucose Via Dipstick

    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+.

    Time frame: From Day -1 through Day 4

  22. Changes From Baseline for Protein Via Dipstick

    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+.

    Time frame: From Day -1 through Day 4

  23. Occurrence of Unsolicited Treatment-emergent Adverse Events

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

    Time frame: From study product administration (Day 1) to Day 8

  24. Occurrence of Treatment-emergent Serious Adverse Events

    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.

    Time frame: From study product administration (Day 1) to Day 8

06

Results

Posted Mar 18, 2019

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.

Participant flow — Overall Study
MilestoneZoliflodacin
Started8
Completed8
Not completed0

Outcome measures

PrimaryMaximum Observed Concentration (Cmax) of Zoliflodacin

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.

Time frame:
From Day 1 to Day 4
Reported as:
Mean · ng/mL
Maximum Observed Concentration (Cmax) of Zoliflodacin
ng/mLZoliflodacin
Maximum Observed Concentration (Cmax) of Zoliflodacin20863 ± 7129
PrimaryTime of Maximum Observed Concentration (Tmax) of Zoliflodacin

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.

Time frame:
From Day 1 to Day 4
Reported as:
Mean · hour
Time of Maximum Observed Concentration (Tmax) of Zoliflodacin
hourZoliflodacin
Time of Maximum Observed Concentration (Tmax) of Zoliflodacin4 ± 3
PrimaryArea Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin

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.

Time frame:
From Day 1 to Day 4
Reported as:
Mean · h x ng/mL
Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin
h x ng/mLZoliflodacin
Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin226750 ± 85336
PrimaryArea Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin

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.

Time frame:
From Day 1 to Day 4
Reported as:
Mean · h x ng/mL
Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin
h x ng/mLZoliflodacin
Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin226500 ± 85340
PrimaryApparent Volume of Distribution (Vz/F) of Zoliflodacin

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.

Time frame:
From Day 1 to Day 4
Reported as:
Mean · Liter
Apparent Volume of Distribution (Vz/F) of Zoliflodacin
LiterZoliflodacin
Apparent Volume of Distribution (Vz/F) of Zoliflodacin183.6 ± 58.8
PrimaryApparent Oral Clearance (CL/F) of Zoliflodacin

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.

Time frame:
Day 1 to Day 4
Reported as:
Mean · L/h
Apparent Oral Clearance (CL/F) of Zoliflodacin
L/hZoliflodacin
Apparent Oral Clearance (CL/F) of Zoliflodacin19.9 ± 7.0
PrimaryElimination Rate Constant (Ke) of Zoliflodacin

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.

Time frame:
From Day 1 to Day 4
Reported as:
Mean · 1/hour
Elimination Rate Constant (Ke) of Zoliflodacin
1/hourZoliflodacin
Elimination Rate Constant (Ke) of Zoliflodacin0.108 ± 0.011
PrimaryTerminal Elimination Half-life (t1/2) of Zoliflodacin

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.

Time frame:
From Day 1 to Day 4
Reported as:
Mean · hour
Terminal Elimination Half-life (t1/2) of Zoliflodacin
hourZoliflodacin
Terminal Elimination Half-life (t1/2) of Zoliflodacin6.5 ± 0.6
SecondaryChanges From Baseline for White Blood Cells With Differentials and Platelets

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · 10^9/L
Changes From Baseline for White Blood Cells With Differentials and Platelets
10^9/LZoliflodacin
Leukocytes-0.659 ± 1.668
Neutrophils-0.118 ± 0.950
Lymphocytes-0.465 ± 0.689
Monocytes-0.036 ± 0.075
Eosinophils-0.035 ± 0.096
Basophils-0.008 ± 0.019
Platelets-7.1 ± 21.9
SecondaryChanges From Baseline Hematocrit

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

Time frame:
From Day -1 through Day 4
Reported as:
Mean · percentage
Changes From Baseline Hematocrit
percentageZoliflodacin
Changes From Baseline Hematocrit1.36 ± 1.68
SecondaryChanges From Baseline Hemoglobin

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

Time frame:
From Day -1 through Day 4
Reported as:
Mean · g/dL
Changes From Baseline Hemoglobin
g/dLZoliflodacin
Changes From Baseline Hemoglobin0.46 ± 0.66
SecondaryChanges From Baseline Red Blood Cell Count

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

Time frame:
From Day -1 through Day 4
Reported as:
Mean · 10^12/L
Changes From Baseline Red Blood Cell Count
10^12/LZoliflodacin
Changes From Baseline Red Blood Cell Count0.150 ± 0.201
SecondaryChanges From Baseline for Albumin and Total Protein

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

Time frame:
From Day -1 through Day 4
Reported as:
Mean · g/dL
Changes From Baseline for Albumin and Total Protein
g/dLZoliflodacin
Albumin0.02 ± 0.23
Total Protein0.11 ± 0.29
SecondaryChange From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)

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

Time frame:
From Day -1 through Day 4
Reported as:
Mean · U/L
Change From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
U/LZoliflodacin
Alkaline Phosphatase-3.1 ± 7.2
Alanine Aminotransferase1.5 ± 4.3
Aspartate Aminotransferase-0.8 ± 2.7
SecondaryChange From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · mg/dL
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin
mg/dLZoliflodacin
BUN-3.0 ± 2.1
Creatinine0.05 ± 0.08
Glucose (fasting)-2.6 ± 3.2
Magnesium-0.01 ± 0.08
Total Bilirubin0.03 ± 0.31
Direct Bilirubin-0.01 ± 0.06
SecondaryChanges From Baseline for Sodium, Potassium, Chloride and Bicarbonate

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · mmol/L
Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate
mmol/LZoliflodacin
Sodium-1.1 ± 1.7
Potassium-0.24 ± 0.36
Chloride-3.6 ± 0.9
Bicarbonate0.5 ± 1.2
SecondaryChanges From Baseline for Blood Pressure - Systolic

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.

Time frame:
From Day -1 through Day 8
Reported as:
Mean · mmHg
Changes From Baseline for Blood Pressure - Systolic
mmHgZoliflodacin
1 Hour1.1 ± 3.9
2 Hour0 ± 5.9
4 Hour-3.9 ± 6.0
Day 2-1.1 ± 5.6
Day 3-3.6 ± 7.4
Day 40.5 ± 6.5
Day 82.4 ± 11.4
SecondaryChanges From Baseline for Blood Pressure - Diastolic

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.

Time frame:
From Day -1 through Day 8
Reported as:
Mean · mmHg
Changes From Baseline for Blood Pressure - Diastolic
mmHgZoliflodacin
1 Hour0.1 ± 5.5
2 Hour-5.3 ± 6.1
4 Hour-4.5 ± 6.3
Day 2-2.8 ± 7.5
Day 3-4.1 ± 6.5
Day 40.0 ± 6.3
Day 8-1.0 ± 10.7
SecondaryChanges From Baseline in Oral Temperature

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.

Time frame:
From Day -1 through Day 8
Reported as:
Mean · Degress C
Changes From Baseline in Oral Temperature
Degress CZoliflodacin
1 Hour-0.04 ± 0.29
2 Hour0.03 ± 0.17
4 Hour0.01 ± 0.24
Day 2-0.06 ± 0.17
Day 3-0.09 ± 0.16
Day 40.06 ± 0.21
Day 8-0.04 ± 0.23
SecondaryChanges From Baseline in Pulse Rate

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.

Time frame:
From Day -1 through Day 8
Reported as:
Mean · Beats per minute
Changes From Baseline in Pulse Rate
Beats per minuteZoliflodacin
1 Hour-3.8 ± 11.7
2 Hour-0.4 ± 14.0
4 Hour-3.5 ± 12.6
Day 2-4.3 ± 12.8
Day 3-1.8 ± 8.7
Day 4-1.9 ± 13.3
Day 81.9 ± 14.0
SecondaryChanges From Baseline for Respiratory Rate

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.

Time frame:
From Day -1 through Day 8
Reported as:
Mean · Breaths per minute
Changes From Baseline for Respiratory Rate
Breaths per minuteZoliflodacin
1 Hour0.3 ± 1.7
2 Hour1.0 ± 2.1
4 Hour0.8 ± 2.4
Day 20.8 ± 1.0
Day 30.5 ± 0.9
Day 40.5 ± 1.4
Day 80.5 ± 1.8
SecondaryChanges From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex)

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · msec
Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex)
msecZoliflodacin
1 Hour4.0 ± 8.6
2 Hour2.3 ± 6.6
4 Hour1.5 ± 7.9
72 Hour6.9 ± 7.7
SecondaryChanges From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave)

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · msec
Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave)
msecZoliflodacin
1 Hour-0.3 ± 3.3
2 Hour0.5 ± 2.7
4 Hour-0.1 ± 2.7
72 Hour1.0 ± 3.9
SecondaryChanges From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula)

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · msec
Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula)
msecZoliflodacin
1 Hour1.8 ± 13.6
2 Hour6.8 ± 13.2
4 Hour4.0 ± 11.6
72 Hour-2.6 ± 11.2
SecondaryChanges From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave)

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · msec
Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave)
msecZoliflodacin
1 Hour-1.1 ± 13.8
2 Hour4.6 ± 15.6
4 Hour3.6 ± 10.8
72 Hour-6.3 ± 8.8
SecondaryChanges 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)

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · msec
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)
msecZoliflodacin
1 Hour-23.3 ± 120.9
2 Hour-20.3 ± 122.3
4 Hour-7.0 ± 64.5
72 Hour-30.1 ± 77.3
SecondaryChanges From Baseline in ECG: Ventricular Rate

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.

Time frame:
From Day -1 through Day 4
Reported as:
Mean · beats per minute
Changes From Baseline in ECG: Ventricular Rate
beats per minuteZoliflodacin
1 Hour1.4 ± 8.0
2 Hour0.9 ± 6.4
4 Hour0.0 ± 3.6
72 Hour1.8 ± 4.9
SecondaryChanges From Baseline for Occult Blood Via Dipstick

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+.

Time frame:
From Day -1 through Day 4
Reported as:
Number · participants
Changes From Baseline for Occult Blood Via Dipstick
participantsZoliflodacin
Changes From Baseline for Occult Blood Via Dipstick0
SecondaryChanges From Baseline for Glucose Via Dipstick

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+.

Time frame:
From Day -1 through Day 4
Reported as:
Count of participants · Participants
Changes From Baseline for Glucose Via Dipstick
ParticipantsZoliflodacin
Changes From Baseline for Glucose Via Dipstick0
SecondaryChanges From Baseline for Protein Via Dipstick

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+.

Time frame:
From Day -1 through Day 4
Reported as:
Count of participants · Participants
Changes From Baseline for Protein Via Dipstick
ParticipantsZoliflodacin
Changes From Baseline for Protein Via Dipstick0
SecondaryOccurrence of Unsolicited Treatment-emergent Adverse Events

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

Time frame:
From study product administration (Day 1) to Day 8
Reported as:
Count of participants · Participants
Occurrence of Unsolicited Treatment-emergent Adverse Events
ParticipantsZoliflodacin
Occurrence of Unsolicited Treatment-emergent Adverse Events8
SecondaryOccurrence of Treatment-emergent Serious Adverse Events

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.

Time frame:
From study product administration (Day 1) to Day 8
Reported as:
Count of participants · Participants
Occurrence of Treatment-emergent Serious Adverse Events
ParticipantsZoliflodacin
Occurrence of Treatment-emergent Serious Adverse Events0

Adverse events

Collected over Unsolicited Adverse Events and serious adverse events (SAEs) were collected from study product administration to Day 8.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Zoliflodacin0/8 (0%)0/8 (0%)8/8 (100%)
Most frequent other events
Most frequent other events
EventZoliflodacin
ELECTROCARDIOGRAM QT PROLONGEDInvestigations6/8
HEART RATE DECREASEDInvestigations4/8
DIARRHOEAGastrointestinal disorders1/8
ABDOMINAL PAINGastrointestinal disorders1/8
NEUTROPHIL COUNT DECREASEDInvestigations1/8
WHITE BLOOD CELL COUNT DECREASEDInvestigations1/8
DERMATITIS CONTACTSkin and subcutaneous tissue disorders1/8

Baseline characteristics

All participants are included in the baseline analysis population.

Age, Categorical
Age, Categorical(Participants)Zoliflodacin
<=18 years0
Between 18 and 65 years8
>=65 years0
Age, Continuous
Age, Continuous(years)Zoliflodacin
Mean26.0 ± 3.6
Sex: Female, Male
Sex: Female, Male(Participants)Zoliflodacin
Female4
Male4
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Zoliflodacin
Hispanic or Latino0
Not Hispanic or Latino8
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Zoliflodacin
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White7
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Zoliflodacin
United States8
Body Mass Index
Body Mass Index(kg/m2)Zoliflodacin
Mean25.50 ± 1.59
07

Study locations

1 site
  • Quintiles Phase I Services - Overland Park
    Overland Park, Kansas 66211-1553, United States
08

References and documents

Study documents

  • Study protocol · Jan 25, 2018
  • Statistical analysis plan · Apr 3, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03404167
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Sponsor
First posted
Jan 19, 2018
Start date
Feb 2, 2018
Primary completion
Mar 2, 2018
Completion
Mar 2, 2018
Results posted
Mar 18, 2019
Last update
Mar 18, 2019

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Gonorrhea→

Other studies from this sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Start the discussion