Healthy Lactating Women
Conditions
Brief summary
Evaluation of the Excretion of Fosfomycin into Breast Milk Following a Single Intravenous Dose of ZTI-01 (6 g) in Healthy Lactating Women
Detailed description
Evaluation of the Excretion of Fosfomycin into Breast Milk Following a Single Intravenous Dose of ZTI-01 (6 g) in Healthy Lactating Women
Interventions
DRUGZTI-01
Participants will receive a single intravenous dose of ZTI-01 (6 g)
Sponsors
Meitheal Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant must be 18 to 45 years of age inclusive, at the time of signing the informed consent. 2. Participant is a healthy lactating female, who is actively breastfeeding (including baby to breast, bottle feeding mother's expressed breast milk) and is at least 12 weeks postpartum of a healthy term (≥ 37 weeks gestational age) newborn infant (no medical complications) and not more than 1 years postpartum. Lactation must be well established prior to the day of admission to inpatient unit. 3. Participant is overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and 12-lead ECG at screening. 4. Participant is willing to temporarily discontinue breastfeeding their infant and discard all their breast milk for 5 consecutive days, including (day of admission to inpatient unit (Day -1), day of dosing while in the inpatient unit (Day 1), and 3 consecutive days after dose (including the day of discharge from the inpatient unit and 2 days at home; Days 2 to 4); and willing to store sufficient amount of breastmilk (e.g., breast milk pumped and stored in freezer before the day of admission), and/or infant formula to feed infant during these 5 consecutive days. 5. Participant must not be in the process of weaning before admission to inpatient unit and have maintained an adequate breast milk supply (according to Investigator discretion) with regularly pumping or routine breastfeeding (e.g., pumping or feeding 3-4 times a day) at admission. 6. Participant has a body mass index (BMI) within the range 18 to 35 kg/m2 (inclusive) 7. Participant is either sexually inactive (abstinent) or, if sexually active, must agree to use/practice one of the acceptable birth control methods listed in Section 10.3 beginning before or during the screening period prior to the first dose, throughout the inpatient stay, and for 3 days following the dose. 8. Signed informed consent as described in Section 10.1.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 9. Willingness to follow protocol defined restrictions and Investigator/staff instructions and protocol procedures. 10. Agrees to use only the emollient or nipple cream recommended by the investigator for use during the sampling period, if needed.
Exclusion criteria
1. Participant is pregnant or plans to become pregnant during the course of the study. 2. Sensitivity to any of the study interventions, or components thereof, or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. 3. History or presence of cardiovascular, respiratory, psychiatric, metabolic, hepatic, renal, gastrointestinal, endocrinological, hematological, oncological, or neurological disorders determined to be clinically significant by the Investigator. 4. History or presence of any condition that in the opinion of the Investigator would constitute a risk when taking the study intervention or interfere with the interpretation of data. 5. History or presence of drug or alcohol abuse or current alcohol use \> 21 units of alcohol per week (1 unit is equal to approximately 330 mL of beer, 1 small glass \[200 mL\] of wine, or 1 measure \[25 mL\] of spirits). 6. History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening with the exception of casual smokers (i.e., \< 5 cigarettes per week). 7. Has history of mastitis within 30 days, breast cancer and/or has had a mastectomy or lumpectomy with the exception of a benign fibroma or lipoma removal at the investigator's discretion; and/or a clinically significant abnormality observed in either breast during a clinical breast exam at Screening or Admission (Day -1). 8. Past or intended use of prescription medication within 14 days or over-the-counter medication including herbal medications within 7 days prior to dosing (apart from vitamin/mineral supplements or occasional paracetamol). 9. Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within 90 days or 5 half-lives (whichever is longer) before planned first dose of study intervention in this clinical study. 10. Positive drug/alcohol screen at screening or Day -1. At screening visit, in case of a positive result the urine screen for drugs of abuse may be repeated once at the discretion of the Investigator. 11. Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies at screening; positive test results for hepatitis B surface antigen (HBsAg), immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc), or hepatitis C virus (HCV Ab) antibodies at screening. 12. Positive pregnancy test at screening or Day -1. 13. Clinically significant vital signs, ECG findings, or laboratory abnormalities, including CrCl ≤ 50 mL/min. 14. Has history of breast implants, breast augmentation, or breast reduction surgery. 15. Unwilling to abstain from alcohol for 48 hours prior to dosing through the duration of confinement. 16. Employees or close relatives of the contract service providers, the sponsor, 3rd party vendors or affiliates of the above mentioned parties. 17. Vulnerable participants (e.g., persons in detention).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve for drug concentrations in breast milk from time 0 to 24 hours (AUC0-24h,milk) | 0-24 hours post dose | To evaluate the PK of ZTI-01 in breast milk in healthy lactating women following a single intravenous dose |
| Maximum observed drug concentration in breast milk (Cmax,milk) | 0-24 hours post dose | To evaluate the PK of ZTI-01 in breast milk in healthy lactating women following a single intravenous dose |
| Time to reach the maximum observed drug concentration in breast milk (Tmax,milk) | 0-24 hours post dose | To evaluate the PK of ZTI-01 in breast milk in healthy lactating women following a single intravenous dose |
| Average drug concentration in breast milk (Cave,milk), calculated as AUC₀-24h, milk divided by Tau (τ) | 0-24 hours post dose | To evaluate the PK of ZTI-01 in breast milk in healthy lactating women following a single intravenous dose |
| Total amount of drug in breast milk over a period of 24 hours (Ammilk, mg/day) following a single dose | 0-24 hours post dose | To evaluate the PK of ZTI-01 in breast milk in healthy lactating women following a single intravenous dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated daily infant dosage (EDID, mg/kg/day) | 0-24 hours post dose | To estimate daily infant dose of ZTI-01 via breast milk |
| Relative infant dose (RID, %) | 0-24 hours post dose | To estimate daily infant dose of ZTI-01 via breast milk |
| Adverse event (AE) assessments | Baseline (Day 1) to End of Study (Day 4) | To assess the safety and tolerability of ZTI-01 in healthy lactating women |
Contacts
CONTACTMeitheal Pharmaceuticals, Inc. Meitheal Pharmaceuticals, Inc.
Outcome results
None listed