Phase 1
Completed N=8
A Study to Evaluate the Safety, Tolerability and Plasma PK of a Single Oral Dose of Zoliflodacin in Healthy Male and Female Volunteers
Source: ClinicalTrials.gov NCT03404167 ↗Enrolled (actual)
8
Serious AEs
0.0%
Results posted
Mar 2019
Primary outcomePrimary: Maximum Observed Concentration (Cmax) of Zoliflodacin — 20863 ng/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Concentration (Cmax) of Zoliflodacin |
20863 | — |
| PRIMARY Time of Maximum Observed Concentration (Tmax) of Zoliflodacin |
4 | — |
| PRIMARY Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Zoliflodacin |
226750 | — |
| PRIMARY Area Under the Concentration Time-curve From Time Zero to the Last Concentration Above the Lower Limit of Quantitation (AUC(0-last)) for Zoliflodacin |
226500 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) of Zoliflodacin |
183.6 | — |
| PRIMARY Apparent Oral Clearance (CL/F) of Zoliflodacin |
19.9 | — |
| PRIMARY Elimination Rate Constant (Ke) of Zoliflodacin |
0.108 | — |
| PRIMARY Terminal Elimination Half-life (t1/2) of Zoliflodacin |
6.5 | — |
| SECONDARY Changes From Baseline for White Blood Cells With Differentials and Platelets |
-0.659; -0.118; -0.465; -0.036; -0.035; -0.008 | — |
| SECONDARY Changes From Baseline Hematocrit |
1.36 | — |
| SECONDARY Changes From Baseline Hemoglobin |
0.46 | — |
| SECONDARY Changes From Baseline Red Blood Cell Count |
0.150 | — |
| SECONDARY Changes From Baseline for Albumin and Total Protein |
0.02; 0.11 | — |
| SECONDARY Change From Baseline for Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) |
-3.1; 1.5; -0.8 | — |
| SECONDARY Change From Baseline for Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose (Fasting at Least 4h), Magnesium, Total and Direct Bilirubin |
-3.0; 0.05; -2.6; -0.01; 0.03; -0.01 | — |
| SECONDARY Changes From Baseline for Sodium, Potassium, Chloride and Bicarbonate |
-1.1; -0.24; -3.6; 0.5 | — |
| SECONDARY Changes From Baseline for Blood Pressure - Systolic |
1.1; 0; -3.9; -1.1; -3.6; 0.5 | — |
| SECONDARY Changes From Baseline for Blood Pressure - Diastolic |
0.1; -5.3; -4.5; -2.8; -4.1; 0.0 | — |
| SECONDARY Changes From Baseline in Oral Temperature |
-0.04; 0.03; 0.01; -0.06; -0.09; 0.06 | — |
| SECONDARY Changes From Baseline in Pulse Rate |
-3.8; -0.4; -3.5; -4.3; -1.8; -1.9 | — |
| SECONDARY Changes From Baseline for Respiratory Rate |
0.3; 1.0; 0.8; 0.8; 0.5; 0.5 | — |
| SECONDARY Changes From Baseline in ECG: PR Interval (Interval From Onset of P-wave to the Onset of the QRS Complex) |
4.0; 2.3; 1.5; 6.9 | — |
| SECONDARY Changes From Baseline in ECG: QRS Duration (Time From the Start of the Q-wave to the End of the S-wave) |
-0.3; 0.5; -0.1; 1.0 | — |
| SECONDARY Changes From Baseline in ECG: QTcF Interval (QT Interval Corrected by Fridericia's Formula) |
1.8; 6.8; 4.0; -2.6 | — |
| SECONDARY Changes From Baseline in ECG: QT Interval (Interval From Onset of the Q-wave to the End of the T-wave) |
-1.1; 4.6; 3.6; -6.3 | — |
| SECONDARY 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) |
-23.3; -20.3; -7.0; -30.1 | — |
| SECONDARY Changes From Baseline in ECG: Ventricular Rate |
1.4; 0.9; 0.0; 1.8 | — |
| SECONDARY Changes From Baseline for Occult Blood Via Dipstick |
— | — |
| SECONDARY Changes From Baseline for Glucose Via Dipstick |
— | — |
| SECONDARY Changes From Baseline for Protein Via Dipstick |
— | — |
| SECONDARY Occurrence of Unsolicited Treatment-emergent Adverse Events |
8 | — |
| SECONDARY Occurrence of Treatment-emergent Serious Adverse Events |
— | — |
Eligibility Criteria
Inclusion Criteria
- 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 / = 50 kg (110 lbs.) and / = 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
Exclusion Criteria
- 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.
- 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 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 ventri
Data sourced from ClinicalTrials.gov (NCT03404167). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.