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

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ClinicalTrials.gov Identifier: NCT03404167
Recruitment Status : Completed
First Posted : January 19, 2018
Last Update Posted : May 30, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Condition or disease Intervention/treatment Phase
Gonorrhoea Drug: AZD0914 Phase 1

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 14, 2018
Actual Primary Completion Date : March 2, 2018
Actual Study Completion Date : March 2, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Gonorrhea

Arm Intervention/treatment
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
Zoliflodacin (also known as AZD0914 and ETX0914), is a spiropyrimidinetrione antibacterial agent




Primary Outcome Measures :
  1. Apparent oral clearance (CL/F) of zoliflodacin measured using a validated HPLC-MS/MS method [ Time Frame: From Day 1 to Day 4 ]
  2. Apparent volume of distribution (Vz/F) of zoliflodacin 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 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 measured using a validated HPLC-MS/MS method [ Time Frame: From Day 1 to Day 4 ]
  5. Area under the concentration time-curve from time zero to time t (AUC(0-t)) for zoliflodacin measured using a validated HPLC-MS/MS method [ Time Frame: From Day 1 to Day 4 ]
  6. Elimination rate constant (Ke) of zoliflodacin measured using a validated HPLC-MS/MS method [ Time Frame: From Day 1 to Day 4 ]
  7. Maximum observed concentration (Cmax) of zoliflodacin 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 measured using a validated HPLC-MS/MS method [ Time Frame: From Day 1 to Day 4 ]
  9. Time of maximum observed concentration (Tmax) of zoliflodacin measured using a validated HPLC-MS/MS method [ Time Frame: From Day 1 to Day 4 ]

Secondary Outcome Measures :
  1. Changes in alanine aminotransferase (ALT) [ Time Frame: From Day 1 through Day 4 ]
  2. Changes in albumin [ Time Frame: From Day 1 through Day 4 ]
  3. Changes in alkaline phosphatase (AP) [ Time Frame: From Day 1 through Day 4 ]
  4. Changes in aspartate aminotransferase (AST) [ Time Frame: From Day 1 through Day 4 ]
  5. Changes in bicarbonate (CO2) [ Time Frame: From Day 1 through Day 4 ]
  6. Changes in Blood Pressure [ Time Frame: From Day 1 through Day 8 ]
  7. Changes in blood urea nitrogen (BUN) [ Time Frame: From Day 1 through Day 4 ]
  8. Changes in chloride [ Time Frame: From Day 1 through Day 4 ]
  9. Changes in direct bilirubin [ Time Frame: From Day 1 through Day 4 ]
  10. Changes in ECG: PR interval measured in sec [ Time Frame: From Day 1 through Day 4 ]
  11. Changes in ECG: QT/QTc interval (Fridericia's correction) measured in msec [ Time Frame: From Day 1 through Day 4 ]
  12. Changes in glucose (fasting at least 4 h) [ Time Frame: From Day 1 through Day 4 ]
  13. Changes in hematocrit (Hct) [ Time Frame: From Day 1 through Day 4 ]
  14. Changes in hemoglobin (Hgb) [ Time Frame: From Day 1 through Day 4 ]
  15. Changes in magnesium [ Time Frame: From Day 1 through Day 4 ]
  16. Changes in Oral temperature [ Time Frame: From Day 1 through Day 8 ]
  17. Changes in platelet count [ Time Frame: From Day 1 through Day 4 ]
  18. Changes in potassium [ Time Frame: From Day 1 through Day 4 ]
  19. Changes in Pulse rate [ Time Frame: From Day 1 through Day 8 ]
  20. Changes in red blood cell (RBC) count [ Time Frame: From Day 1 through Day 4 ]
  21. Changes in Respiratory rate [ Time Frame: From Day 1 through Day 8 ]
  22. Changes in routine dipstick testing of clean-catch urine for glucose [ Time Frame: From Day 1 through Day 4 ]
  23. Changes in routine dipstick testing of clean-catch urine for protein [ Time Frame: From Day 1 through Day 4 ]
  24. Changes in routine dipstick testing of clean-catch urine for blood [ Time Frame: From Day 1 through Day 4 ]
  25. Changes in serum creatinine, with estimation of GFR [ Time Frame: From Day 1 through Day 4 ]
  26. Changes in sodium [ Time Frame: From Day 1 through Day 4 ]
  27. Changes in total bilirubin [ Time Frame: From Day 1 through Day 4 ]
  28. Changes in total protein [ Time Frame: From Day 1 through Day 4 ]
  29. Changes in white blood cell (WBC) count with absolute differential count [ Time Frame: From Day 1 through Day 4 ]
  30. Occurrence of treatment-emergent SAEs [ Time Frame: Up to Day 8 ]
  31. Occurrence of unsolicited treatment-emergent AEs [ Time Frame: Up to Day 8 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03404167


Locations
United States, Kansas
Quintiles Phase I Services - Overland Park
Overland Park, Kansas, United States, 66211-1553
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03404167     History of Changes
Other Study ID Numbers: 16-0118
HHSN272201500005I
First Posted: January 19, 2018    Key Record Dates
Last Update Posted: May 30, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
ETX0914
Plasma Pharmacokinetic
Safety
Tolerability
Zoliflodacin

Additional relevant MeSH terms:
Gonorrhea
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Sexually Transmitted Diseases, Bacterial
Sexually Transmitted Diseases
Infection
Genital Diseases, Male
Genital Diseases, Female