A Study to Evaluate the Safety, Tolerability and Plasma PK of a Single Oral Dose of Zoliflodacin in Healthy Male and Female Volunteers
Condition: Gonorrhoea
MeSH terms: Gonorrhea
Intervention: AZD0914
Intervention description: Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent
Intervention MeSH terms: Zoliflodacin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ETX0914; Plasma Pharmacokinetic; Safety; Tolerability; Zoliflodacin

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.
    

Eligibility criteria:

        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:

        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

          -  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