GonorrhoeaPhase 1NCT03404167
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 study testing AZD0914 in people with Gonorrhoea, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Gonorrhoea
- What is being tested?
- AZD0914
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Feb 2018to 2 Mar 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Informed consent form (ICF) understood and signed before initiating any study procedures
- Healthy male or female, as assessed by the authorized site clinician (listed on FDA Form 1572)
- 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
- Aged 18 to 45 years inclusive on the day of study drug dosing
- Body Mass Index (BMI) > / = 18.5 and < / = 30 kg/m^2 and weight > / = 50 kg (110 lbs.) and < / = 100 kg (220 lbs.)
- In female subjects of childbearing potential, a negative serum pregnancy test at Screening Visit and on Day -1
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- 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)
- If female, not pregnant, not breast feeding, and not planning on becoming pregnant during the trial and for 30 days after study participation
- 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
- Male subjects must agree to refrain from sperm donation for the duration of the trial and for 90 days after Final Visit
- Laboratory tests are in the normal reference range with acceptable exceptions
- Vital signs are within the acceptable range
- Has adequate venous access for blood collection
- Urine drug screen is negative for tested substances
- Alcohol test (breathalyzer) is negative
- Willing to abstain from alcohol consumption for 2 days before Day -1 and during the trial
Who cannot join
- 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.
- 2) 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
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- 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.
- 14) 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Quintiles Phase I Services - Overland Park
Overland Park, Kansas, 66211-1553
About this study
Official title: A Phase 1 Clinical Trial to Evaluate the Plasma Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Zoliflodacin in Healthy Male and Female Subjects
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.
- Conditions
- Gonorrhoea
- Being tested
- AZD0914
- Keywords
- ETX0914, Plasma Pharmacokinetic, Safety, Tolerability, Zoliflodacin
- Medical subject headings
- Gonorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0914Drug
Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
| Study group | Role | What they receive |
|---|---|---|
| Zoliflodacin | Experimental | 4 g (2 sachets of 2 g) of zoliflodacin orally in the morning of Day 1 after 8 hours of fasting, n=8 Receives: Drug: AZD0914 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Day 1 to Day 4
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.
Measured: From Day 1 to Day 4
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.
Measured: From Day 1 to Day 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.
Measured: From Day 1 to Day 4
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.
Measured: From Day 1 to Day 4
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.
Measured: Day 1 to Day 4
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.
Measured: From Day 1 to Day 4
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.
Measured: From Day 1 to Day 4
Secondary outcomes (24)
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.
Measured: From Day -1 through Day 4
Changes From Baseline Hematocrit
Change from baseline calculated by subtracting the Day -1 (baseline) hematocrit measurement from the Day 4 hematocrit measurement.
Measured: From Day -1 through Day 4
Changes From Baseline Hemoglobin
Change from baseline calculated by subtracting the Day -1 (baseline) hemoglobin measurement from the Day 4 hemoglobin measurement.
Measured: From Day -1 through Day 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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 8
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.
Measured: From Day -1 through Day 8
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.
Measured: From Day -1 through Day 8
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.
Measured: From Day -1 through Day 8
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.
Measured: From Day -1 through Day 8
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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.
Measured: From Day -1 through Day 4
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+.
Measured: From Day -1 through Day 4
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+.
Measured: From Day -1 through Day 4
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+.
Measured: From Day -1 through Day 4
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.
Measured: From study product administration (Day 1) to Day 8
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.
Measured: From study product administration (Day 1) to Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2018
- Study start2 Feb 2018
- Primary completion2 Mar 2018
- Study completion2 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GonorrhoeaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03404167
- Sponsor's protocol ID
- 16-0118
- Other IDs
- HHSN272201500005I
- Status last verified
- 11 Jan 2018
- First submitted
- 4 Jan 2018
- Last updated
- 18 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Clinical Trial to Evaluate the Plasma Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Zoliflodacin in Healthy Male and Female Subjects
- ClinicalTrials.gov ID
- NCT03404167
- Acronym / sponsor ID
- 16-0118
- Conditions
- Gonorrhoea
- Keywords
- ETX0914, Plasma Pharmacokinetic, Safety, Tolerability, Zoliflodacin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 2 Feb 2018 (actual)
- Primary completion
- 2 Mar 2018 (actual)
- Study completion
- 2 Mar 2018 (actual)
- First posted
- 19 Jan 2018 (actual)
- Results
- Posted 18 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zoliflodacin | Experimental | Drug: AZD09144 g (2 sachets of 2 g) of zoliflodacin orally in the morning of Day 1 after 8 hours of fasting, n=8 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Informed consent form (ICF) understood and signed before initiating any study procedures
- Healthy male or female, as assessed by the authorized site clinician (listed on FDA Form 1572)
- 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
- Aged 18 to 45 years inclusive on the day of study drug dosing
- Body Mass Index (BMI) > / = 18.5 and < / = 30 kg/m^2 and weight > / = 50 kg (110 lbs.) and < / = 100 kg (220 lbs.)
Key exclusion criteria (15 listed)
- 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.
- 2) 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD0914Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent | Drug | Zoliflodacin |
Primary outcome
Maximum Observed Concentration (Cmax) of Zoliflodacin
Time frame: From Day 1 to Day 4
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 of Maximum Observed Concentration (Tmax) of Zoliflodacin
Time frame: From Day 1 to Day 4
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.
Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin
Time frame: From Day 1 to Day 4
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.
Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin
Time frame: From Day 1 to Day 4
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.
Apparent Volume of Distribution (Vz/F) of Zoliflodacin
Time frame: From Day 1 to Day 4
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.
Apparent Oral Clearance (CL/F) of Zoliflodacin
Time frame: Day 1 to Day 4
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.
Elimination Rate Constant (Ke) of Zoliflodacin
Time frame: From Day 1 to Day 4
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.
Terminal Elimination Half-life (t1/2) of Zoliflodacin
Time frame: From Day 1 to Day 4
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.
24 secondary outcomes
Changes From Baseline for White Blood Cells With Differentials and Platelets
Time frame: From Day -1 through Day 4
Changes From Baseline Hematocrit
Time frame: From Day -1 through Day 4
Changes From Baseline Hemoglobin
Time frame: From Day -1 through Day 4
Changes From Baseline Red Blood Cell Count
Time frame: From Day -1 through Day 4
Changes From Baseline for Albumin and Total Protein
Time frame: From Day -1 through Day 4
Change From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
Time frame: From Day -1 through Day 4
Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin
Time frame: From Day -1 through Day 4
Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate
Time frame: From Day -1 through Day 4
Changes From Baseline for Blood Pressure - Systolic
Time frame: From Day -1 through Day 8
Changes From Baseline for Blood Pressure - Diastolic
Time frame: From Day -1 through Day 8
Changes From Baseline in Oral Temperature
Time frame: From Day -1 through Day 8
Changes From Baseline in Pulse Rate
Time frame: From Day -1 through Day 8
Changes From Baseline for Respiratory Rate
Time frame: From Day -1 through Day 8
Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex)
Time frame: From Day -1 through Day 4
Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave)
Time frame: From Day -1 through Day 4
Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula)
Time frame: From Day -1 through Day 4
Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave)
Time frame: From Day -1 through Day 4
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)
Time frame: From Day -1 through Day 4
Changes From Baseline in ECG: Ventricular Rate
Time frame: From Day -1 through Day 4
Changes From Baseline for Occult Blood Via Dipstick
Time frame: From Day -1 through Day 4
Changes From Baseline for Glucose Via Dipstick
Time frame: From Day -1 through Day 4
Changes From Baseline for Protein Via Dipstick
Time frame: From Day -1 through Day 4
Occurrence of Unsolicited Treatment-emergent Adverse Events
Time frame: From study product administration (Day 1) to Day 8
Occurrence of Treatment-emergent Serious Adverse Events
Time frame: From study product administration (Day 1) to Day 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD0914 in people with Gonorrhoea, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Observed Concentration (Cmax) of Zoliflodacin (time frame: From Day 1 to Day 4). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2019.