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AzTrials

Electrocardiogram Repolarisation AbnormalityPhase 1NCT03613649

Thorough QT/QTC (TQT) Clinical Trial to Evaluate the Effect of Zoliflodacin on Cardiac Repolarization in Healthy Male and Female Subjects

A Phase 1 study testing AZD0914 and Moxifloxacin in people with Electrocardiogram Repolarisation Abnormality and Gonococcal Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The Phase I Thorough QT/QTc (TQT) study will be performed in a single center, the Vince \& Associates Clinical Research, Inc., clinical trials unit (CTU), in 72 healthy male or female subjects, aged 18 to 45 years inclusive, to evaluate the effect of zoliflodacin on the corrected QT interval of the electrocardiogram… Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
What is being tested?
AZD0914 and Moxifloxacin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
72 participants
Where
1 siteUnited States
Study dates
25 Sep 2018to 2 Jan 2019
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

  • All must be answered YES for the subject to be eligible for study participation:
  • Informed consent form (ICF) understood and signed before initiating any study procedures
  • Healthy male or female, as assessed by authorized site clinician (listed on FDA Form 1572)
  • Willingness to comply with and be available for all protocol procedures, including inpatient confinement for 3 days in each dosing period and follow-up for the duration of the trial
  • Aged 18 to 45 years inclusive on the day of first dosing
  • Body Mass Index (BMI) > / = 18.5 and < / = to 30 kg per m^2 and weight > / = 50 kg (110 lbs.) and < / = 100 kg (220 lbs.)
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  • In all female subjects, whether of childbearing potential or post-menopausal by medical history (MH), a negative serum pregnancy test at Screening Visit and on Day -1 of each dosing period
  • -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 to become pregnant during the trial and for 30 days after Final Visit
  • 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 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 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 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 (VS) are within the acceptable range
  • Has adequate venous access for blood collection
  • Urine drug screen is negative for tested substances
  • Urine alcohol test is negative
  • Willing to abstain from alcohol consumption for 2 days before Day -1 of Period 1 and for the duration of the trial

Who cannot join

  • All must be answered NO for the subject to be eligible for study participation:
  • 1. History of acute or chronic cardiovascular disease or surgery
  • Note: Conditions include: congestive heart failure; coronary artery disease (myocardial infarction, unstable angina); cerebrovascular disease (cerebrovascular accident or stroke or transient ischemic attack (TIA); chronic hypertension; or coronary revascularization surgery (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) 2. History of cardiac arrhythmia or syncope related to cardiac arrhythmia or unexplained, or use of a cardiac pacemaker
  • Note: Conditions include: atrial fibrillation, atrial flutter, or non-sustained or sustained ventricular tachycardia; use of a cardiac pacemaker; personal or family history of LQTS; or family history of sudden death 3. History of any other 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; 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 surgery including weight loss surgery or biliary surgery 4. Major surgical interventions are not permitted within 4 weeks of first dosing and during the trial. Minor surgical interventions are not allowed within 2 weeks of first dosing and during the trial 5. 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 6. Active allergic symptoms to seasonal and animal allergens that are moderate to severe, affect daily activity, and require continuous treatment 7. A marked baseline prolongation of ECG intervals, or HR less than 45 bpm or greater than 100 bpm on ECG measurements
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  • Note: The following are considered prolonged ECG intervals: QTc/QTcF > 449 msec in males and females; PR > 209 msec; and QRS > 110 msec 8. 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; any characteristics that would make QT assessment unreliable, including flat T waves; or any condition deemed clinically significant by a study investigator 9. 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 10. Positive serology results for HIV, HBsAg, or HCV 11. Febrile illness with temperature > / = 38.0 degrees Celsius for < 7 days before dosing in each treatment period 12. Donated whole blood or blood products within 60 days before first dosing, or plans to donate or receive before Final Visit (Day 8 + / - 2 after last dose in dosing period 4)
  • Note: Blood products include RBCs, white blood cells (WBCs), platelets, and plasma 13. Known allergic reactions to fluoroquinolones or to components present in the formulation or processing of zoliflodacin and moxifloxacin 14. Treatment with another investigational product within 30 days of first 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 15. Active drug or alcohol binge consumption, abuse, or dependence within 12 months before Screening Visit that, in the opinion of the investigator, would interfere with adherence to study requirements 16. Use of any prescription medication within 30 days before first dosing or planned use during the trial except as noted below and approved by the designated study clinician
  • Note 1: Prohibited medications include moderate or strong CYP3A4 inducers and other drugs with known risk for QT prolongation and TdP; 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 up to 7 days before first dosing or 7 days after last dosing
  • Note 2: Allowed medications include: oral contraceptives; H1 antihistamines; all medications approved for control of intraocular pressure including topical ophthalmic non-selective beta-blockers, such as betaxolol, carteolol, levobunolol, metipranolol, and timolol; topical/ intranasal corticosteroids; nonsteroidal anti-inflammatory drugs (NSAIDS); licensed influenza vaccine during the flu season, 7 days before first dosing or 7 days after last dosing 17. Use of non-prescription medications, vitamins, herbs, or nutritional supplements within 15 days before first dosing or planned use during the trial unless approved by the study clinician
  • Note 1: Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug-metabolizing enzymes and transporters (e.g., grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard], and charbroiled meats) within 7 days before dosing
  • Note 2: Exceptions: St. John's wart is not allowed within 30 days of dosing; vitamins and over-the-counter (OTC) medications taken for a brief period (less than 48 h) for the treatment of common symptoms (such as headache, indigestion, muscle pain) may be allowed as approved by the designated study clinician 18. Intake of caffeinated beverages or food within 72 h before first dosing or a history of high caffeine consumption (e.g., in the last 4 months drinking > 5 cups of coffee/day) 19. Smoking or use of tobacco or nicotine-containing products within 30 days before first dosing 20. Engagement in strenuous exercise within 15 days before first dosing (e.g., marathon running, long-distance cycling, weight lifting) and during the trial 21. 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 22. 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 trial
  • Note: Includes trials that have a study intervention such as a drug, biologic, or device 23. Is a CTU employee or staff member who is paid entirely or partially by the Office of Clinical Research Resources (OCRR)/NIAID contract for the DMID-funded trial
  • Note: CTU 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

  • Vince and Associates Clinical Research

    Overland Park, Kansas, 66212

Other trials in United States

About this study

Official title: A Phase 1, Randomized, Double-blinded, Four-period Crossover, Thorough QT/QTC (TQT) Clinical Trial to Evaluate the Effect of Zoliflodacin on Cardiac Repolarization in Healthy Male and Female Subjects

The Phase I Thorough QT/QTc (TQT) study will be performed in a single center, the Vince \& Associates Clinical Research, Inc., clinical trials unit (CTU), in 72 healthy male or female subjects, aged 18 to 45 years inclusive, to evaluate the effect of zoliflodacin on the corrected QT interval of the electrocardiogram (ECG) using Fridericia's Formula (QTcF) and other ECG parameters; the correlation of the drug concentrations (and pharmacokinetic (PK) profile) with time-matched, placebo-corrected, baseline-adjusted difference in QTcF interval (delta delta QTcF); and the PK and safety profiles of the new zoliflodacin formulation. Each subject will receive one dose of each of four treatments: zoliflodacin 2 g orally, zoliflodacin 4 g orally, placebo for zoliflodacin 4 g orally, and moxifloxacin 400 mg orally. The study will last approximately 12 weeks with a subject participation duration of up to 55 days. The primary hypothesis to be tested is that following administration of zoliflodacin 2 g and 4 g, the upper bound of the one-sided 95% confidence interval (CI) of treatment effect on delta delta QTcF is > / = 10 msec for at least one of the ECG assessments, against the alternative hypothesis that all mean effects are < 10 msec. The primary objective is to evaluate the effect of zoliflodacin on the corrected QT interval of the ECG using Fridericia's formula (QTcF).

Read the detailed description

The Phase I Thorough QT/QTc (TQT) study will be performed in a single center, the Vince \& Associates Clinical Research, Inc., clinical trials unit (CTU), according to a randomized, double-blinded (except for the use of moxifloxacin), placebo-controlled, four-period, four-treatment, crossover design balanced with respect to first-order carryover effect in 72 healthy male or female subjects, aged 18 to 45 years inclusive, to evaluate the effect of zoliflodacin on the corrected QT interval of the electrocardiogram (ECG) using Fridericia's Formula (QTcF) and other ECG parameters; the correlation of the drug concentrations (and pharmacokinetic (PK) profile) with time-matched, placebo-corrected, baseline-adjusted difference in QTcF interval (delta delta QTcF); and the PK and safety profiles of the new zoliflodacin formulation. Each subject will receive one dose of each of four treatments: zoliflodacin 2 g orally, zoliflodacin 4 g orally, placebo for zoliflodacin 4 g orally, and moxifloxacin 400 mg orally. The study will last approximately 12 weeks with a subject participation duration of up to 55 days. The primary hypothesis to be tested is that following administration of zoliflodacin 2 g and 4 g, the upper bound of the one-sided 95% confidence interval (CI) of treatment effect on delta delta QTcF is > / = 10 msec for at least one of the ECG assessments, against the alternative hypothesis that all mean effects are < 10 msec. The primary objective is to evaluate the effect of zoliflodacin on the corrected QT interval of the ECG using Fridericia's formula (QTcF). The secondary objectives are: 1) to evaluate the effects of zoliflodacin on other ECG parameters (PR, QRS, and RR intervals, and heart rate (HR)); 2) to evaluate the sensitivity of QTcF measurement using moxifloxacin; 3) to evaluate the effect of zoliflodacin on T-wave morphology; 4) to evaluate the PK of 2 g and 4 g oral zoliflodacin under fasting state; 5) to evaluate the relationship between zoliflodacin PK and time-matched QTcF pharmacodynamics (PD); 6) to evaluate the safety and tolerability of 2 g and 4 g oral zoliflodacin.

Being tested
AZD0914, Moxifloxacin, Placebo
Keywords
AZD0914, Cardiac, ETX0914, Healthy, Moxifloxacin, Repolarization, Study, TQT, Volunteers, 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

    Spiropyrimidinetrione antibacterial drug, which inhibits bacterial DNA synthesis by a novel mechanism. Powder will be reconstituted in 60 mL of tap water and dosed orally after an overnight fast. After the cup containing 60 mL of zoliflodacin is taken, approximately 60 mL of tap water will be added to the cup and consumed by the subject to chase the initial dose.

  • MoxifloxacinDrug

    Broad-spectrum 8-methoxy fluoroquinolone with activity against both Gram-positive and Gram-negative bacteria, including anaerobes. A single, commercially-available, film-coated, 400-mg tablet of moxifloxacin hydrochloride will be administered orally with 120 mL of tap water.

  • PlaceboOther

    Composed of 4 g of the same excipients found in zoliflodacin. Powder will be reconstituted in 60 mL of tap water and dosed orally after an overnight fast. After the cup containing 60 mL of placebo is taken, approximately 60 mL of tap water will be added to the cup and consumed by the subject to chase the initial dose.

Study groups in NCT03613649
Study groupRoleWhat they receive
Treatment AExperimental2 g of zoliflodacin administered orally on Day 1 of each dosing period, n=72
Receives: Drug: AZD0914
Treatment BExperimental4 g of zoliflodacin administered orally on Day 1 of each dosing period, n=72
Receives: Drug: AZD0914
Treatment CPlacebo comparatorPlacebo for zoliflodacin administered orally on Day 1 of each dosing period, n=72
Receives: Other: Placebo
Treatment DActive comparator400 mg of moxifloxacin administered orally on Day 1 of each dosing period, n=72
Receives: Drug: Moxifloxacin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The One-sided 95% Confidence Interval (CI) for the Largest Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin

    Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QTcF intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

    Measured: Baseline, 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose after 2 and 4 g zolifloadacin

Secondary outcomes (35)

  1. Time-matched, Placebo-corrected, Baseline-adjusted Heart Rate (HR) Following Administration of Zoliflodacin

    Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline heart rate by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  2. Time-matched, Placebo-corrected, Baseline-adjusted, the Time From the Onset of the P Wave to the Start of the QRS Complex (PR Interval) Following Administration of Zoliflodacin

    Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline PR intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  3. Time-matched, Placebo-corrected, Baseline-adjusted the Time Elapsed Between Two Successive R Waves of the QRS (RR Interval) Following Administration of Zoliflodacin

    Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline RR intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  4. Time-matched, Placebo-corrected, Baseline-adjusted QRS Duration Following Administration of Zoliflodacin

    Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QRS durations by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  5. The One-sided 95% Confidence Interval (CI) of the Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) After a Single Dose of Moxifloxacin

    Mean and 90% two-sided confidence intervals (t-intervals) of change from baseline QTcF intervals by time point and treatment. Note that the upper bound of the 90% two-sided confidence interval can also be interpreted as the upper bound of a 95% one-sided confidence interval.

    Measured: Baseline, 1 h, 2 h, 3 h, and 4 h post-dose

  6. Incidence of Abnormal T-wave Morphology Following Administration of Zoliflodacin

    Categorical T-wave morphology analysis was collected in three ECG replicates at each timepoint (Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose). Abnormalities present in any one or more of the baseline timepoint replicate ECGs recorded for a particular period was considered to be present at baseline for post-dose ECGs from that specific period. If a subject had an ECG morphological abnormality in more than one replicate ECG of a study timepoint, the subject was counted only once for that timepoint. Flat is defined as T amplitude <1 mm (either positive or negative) including flat isoelectric line and Biphasic is defined as T-wave that contains a second component with an opposite phase that was at least 0.1 millivolts (mV) deep (both positive and negative/positive and polyphasic T-waves included).

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  7. 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. Pharmacokinetic (PK) parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

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

    Tmax is 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. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

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

    AUC(0 - infinity) 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 - infinity) 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. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  10. 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. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  11. 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. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  12. 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-infinity) computed from concentrations that were measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  13. 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. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  14. 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. PK parameters were computed using plasma concentrations from samples collected pre-dose and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  15. Relationship Between Plasma Concentrations of Zoliflodacin and Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin

    One-sided 95% confidence intervals of population mean QTcF time-matched, placebo-corrected, baseline-adjusted mean QTcF interval at plasma concentration corresponding to the observed geometric mean Cmax for 2 g and 4 g doses of zoliflodacin were computed using a linear mixed effect model with PK and concentration data collected at baseline and intervals post-dose.

    Measured: Baseline, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose

  16. Number of Participants With Treatment-emergent Serious Adverse Events Following Administration of Zoliflodacin and Moxifloxacin

    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) through prior to the next dose (Day 8 or Final visit).

  17. Number of Participants With Treatment-emergent Adverse Events Following Administration of Study Product

    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) through prior to the next dose (Day 8 or Final visit).

  18. Changes From Baseline for Blood Pressure - Systolic

    Change from baseline in systolic blood pressure was 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 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

    Measured: From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

  19. Changes From Baseline for Blood Pressure - Diastolic

    Change from baseline in diastolic blood pressure was 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 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

    Measured: From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

  20. Changes From Baseline for Pulse Rate

    Change from baseline in pulse rate was 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 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

    Measured: From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

  21. Changes From Baseline for Respiratory Rate

    Change from baseline in respiratory rate was 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 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

    Measured: From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

  22. Changes From Baseline for Temperature

    Change from baseline for temperature was 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 24 h after dosing. Follow up is defined as the check in visit for the next dosing period or the final visit.

    Measured: From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

  23. Changes From Baseline for White Blood Cells With Differentials

    Change from baseline calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Hematology parameters included white blood cell count, and differential (absolute counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils).

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  24. Changes From Baseline for Hemoglobin

    Change from baseline for hemoglobin is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  25. Changes From Baseline for Hematocrit

    Change from baseline for hematocrit is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  26. Changes From Baseline for Erythrocytes

    Change from baseline for erythrocytes is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  27. Changes From Baseline for Platelets

    Change from baseline for platelets is calculated by subtracting the Day -1 (baseline) hematology measurement from the 24 h post dose, and a follow up hematology measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

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

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included sodium, potassium. chloride and bicarbonate.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  29. Changes From Baseline for Magnesium, Glucose (Fasting), Blood Urea Nitrogen (BUN), Creatinine, Total Bilirubin, Direct Bilirubin

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included magnesium, glucose (fasting), BUN, creatinine, total bilirubin, direct bilirubin

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  30. Changes From Baseline for Total Protein and Albumin

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included total protein and albumin.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

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

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit. Chemistry parameters included AST, ALT and AP.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  32. Changes From Baseline for Glomerular Filtration Rate (GFR) - Estimated

    Change from baseline calculated by subtracting the Day -1 (baseline) chemistry measurement from the 24 h post dose, and a follow up chemistry measurement. Follow up is defined as either the check-in visit for the next period or the final visit.

    Measured: Prior to dosing, 24 hour post dose through prior to the next dose (Day 8 or Final visit).

  33. Occurrence of Urinalysis Adverse Events Following Administration of Study Product

    Urine for the clinical laboratory test was collected on Day -1, 24 hour post dose and the check in for the following dosing period. The results for glucose dipstick, protein dipstick and occult blood - dipstick were reported in categorical results. The possibilities were negative, trace, 1+, 2+, and 3+. If the dipsticks were 1+ or greater, microscopic evaluations were performed for erythrocytes, leukocytes and bacteria. For microscopic results to be deemed abnormal, the results must be reported 6 or greater per high power field.

    Measured: From study product administration (Day 1) through prior to the next dose (Day 8 or Final visit).

  34. Changes From Baseline in ECG Measures: PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval

    Change from baseline in ECG is calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, 24 h after dosing and prior to the next dose (follow up). The following ECG Parameters were analyzed: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex), QRS Duration (Time From the Start of the Q-wave to the End of the S-wave), QT Interval (Interval From Onset of the Q-wave to the End of the T-wave), QTcF Interval (QT Interval Corrected by Fridericia's Formula) and 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).

    Measured: Baseline, 1 h, 2 h, 4h, 24 h post-dose and follow up

  35. Changes From Baseline in ECG Measures: Ventricular Rate

    Change from baseline in ECG Ventricular Rate is calculated by subtracting the baseline (pre-dose) measurement from the post-dose measurement. Post-dose measurements were taken 1 h, 2 h, 4 h, 24 h after dosing and prior to the next dose (follow up).

    Measured: Baseline, 1 h, 2 h, 4h, 24 h post-dose and follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2018
  2. Study start25 Sep 2018
  3. Primary completion2 Jan 2019
  4. Study completion2 Jan 2019

Resources

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
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03613649
Sponsor's protocol ID
16-0110
Other IDs
HHSN272201500005I
Status last verified
7 May 2019
First submitted
26 Jul 2018
Last updated
27 Mar 2020
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Newman LM, Kankam M, Nakamura A, Conrad T, Mueller J, O'Donnell J, Osborn BL, Gu K, Saviolakis GA. Thorough QT Study To Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults. Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0129221. doi: 10.1128/AAC.01292-21. Epub 2021 Oct 4.

    PubMed 34606332

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD0914 and Moxifloxacin in people with Electrocardiogram Repolarisation Abnormality and Gonococcal Infection, 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 18 inclusion and 17 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 27 Mar 2020. 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. Some participants in this study may receive a placebo. 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 27 Mar 2020). 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?

The One-sided 95% Confidence Interval (CI) for the Largest Time-matched, Placebo-corrected, Baseline-adjusted Mean QTcF Interval (Delta Delta QTcF) Following Administration of Zoliflodacin (time frame: Baseline, 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-dose after 2 and 4 g zolifloadacin). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03613649, which also lists 1 linked publication.

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 27 Mar 2020.

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