PK Study of Single-Dose ZTI-01 in Children (<12 Years of Age) (Pediatric_PK)

Phase 1, Non-comparative, Open-Label Study of Pharmacokinetics and Safety of a Single-Dose of ZTI-01 (Fosfomycin for Injection) in Pediatric Subjects (<12 Years of Age)

Phase 1 study, a single dose of ZTI-01 given to pediatric subjects (under 12 years of age) who require antibiotic therapy to see what the body does to the drug (pharmacokinetics) and to compare if these effects are similar to those observed in adults at a 6g ZTI-01 dose. Study will help establish pediatric dosing in younger children by age cohort. This is a multiple-center, open-label, PK study of ZTI-01 (fosfomycin for injection) single dose scaled by allometric weight-modeling from an adult ZTI-01 dose of 6 grams. Eligible subjects must be receiving standard of care antibiotics for proven or suspected bacterial infection or for peri-operative prophylaxis surgery (in or out of hospital).

Study Overview

• Status: Recruiting
• Conditions: Pediatric ALL
• Intervention / Treatment: Drug: ZTI-01 100 mg/kg; Drug: ZTI-01 75 mg/kg

Detailed Description

Based on pre-dose weight on Day -1, subjects weighing within the 3rd to < 97th percentile based on age - will receive a single, weight adjusted dose of ZTI-01 via continuous IV infusion or syringe pump over a 1- hour (+10 min) period. Pediatric subjects participating in this study will be assigned to one of three cohorts based on age:

Cohort 1: ≥ 6 years to <12 years (n=6 PK evaluable subjects) Cohort 2: ≥ 2 years to <6 years (n=6 PK evaluable subjects)

Cohort 3: Birth to < 2 years (n=9 PK evaluable subjects), split into 3 subgroups:

(3a) Birth (defined as full term: 37 weeks of gestations or greater) to < 3 mos, (3b) ≥ 3 mos to < 6 mos, (3c) ≥ 6 mos to < 24 months

Cohorts 1 and 2 will be enrolled first with safety and PK data evaluated before enrolling the youngest Cohort 3. Blood for fosfomycin concentration measurement will be collected throughout the study. Safety will be assessed by monitoring adverse and serious adverse events based on medical history, vital signs, ECG, laboratory assessment and physical examination.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Steve Gelone; Phone Number: 6108166641; Email: Steve.Gelone@nabriva.com

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
    • San Diego, California, United States, 92123
      • Recruiting
      • Rady Children's Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Kosair Charities Pediatric Clinical Research Unit
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Children's Hospital of Michigan
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Recruiting
      • University of New Mexico Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed consent/assent
• Male or female subjects aged from Birth (defined as full term: 37 weeks of gestation or greater) but less than 12 years old
• Hospitalized, currently receiving antibacterial treatment for confirmed or suspected bacterial infection
• If of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner from the time of consent through 24 hours after completion of study drug administration
• Has sufficient intravascular access to receive study drug through peripheral or central line

Exclusion Criteria:

• Has history of known allergy, hypersensitivity, or intolerance to oral or intravenous fosfomycin
• Screening serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x ULN or total bilirubin >2x ULN
• Female is post onset of menarche and currently pregnant, or breast feeding, or has a positive serum or urine β-human chorionic gonadotropin (β-hCG) pregnancy test
• Impaired renal function at screening based on the Revised Schwartz Formula using actual body height
• Known infection with immunodeficiency virus (HIV), hepatitis C virus, or hepatitis B virus
• Other laboratory tests, obtained as standard of care, that are outside the normal limits, considered by the Investigator, to be clinically significant
• Have surgery scheduled during collection period of plasma for fosfomycin concentrations
• Weighs outside of the 3rd to less than <97th percentile based on age
• History of a seizure disorder requiring ongoing treatment with anticonvulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years
• Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) of administration of the study drug
• Has enrolled previously in the current trial or has received ZTI-01 or fosfomycin (IV or oral) for any other reason within the last 30 days
• Is expected to survive less than 72 hours after completion of study drug administration
• Plans to use cardiopulmonary bypass, extracorporeal membrane oxygenation, hemodialysis, or peritoneal dialysis during the study
• Clinically significant abnormalities on the ECG; or have or be at risk for major cardiac events or dysfunction including QTc prolongation, clinically unstable cardiac disease, receipt within 24 hours before the start of study drug of a medication that is labelled to prolong the QT interval, and for breastfed infant subjects only - receipt by the subject's mother within 24 hours before the start of study drug of a medication that is labelled to prolong the QT interval
• Planned blood transfusion within 24 hours of study drug administration or expected before the end of the PK sampling, or has had significant blood loss (≥5% of total blood volume) within 4 weeks before the screening visit
• Any condition that, in the opinion of the PI, would compromise the safety of the subject or the quality of the data
• Subject or caregiver/parent is unable or unwilling to adhere to the study-specified procedures and restrictions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZTI-01 Cohort 1 ≥ 6 to <12 years of age; ZTI-01 (fosfomycin IV) 100 mg/kg (single dose) Subjects weighing within the 3rd to < 97th percentile for age	Drug: ZTI-01 100 mg/kg; ZTI-01 intravenous (IV); Other Names: IV fosfomycin; fosfomycin disodium; fosfomycin for injection
Experimental: ZTI-01 Cohort 2 ≥ 2 to <6 years of age; ZTI-01 (fosfomycin IV) 100 mg/kg (single dose) Subjects weighing within the 3rd to < 97th percentile for age	Drug: ZTI-01 100 mg/kg; ZTI-01 intravenous (IV); Other Names: IV fosfomycin; fosfomycin disodium; fosfomycin for injection
Experimental: ZTI-01 Cohort 3a Birth to < 3 mos of age; ZTI-01 (fosfomycin IV) 75 mg/kg (single dose) Subjects weighing within the 3rd to < 97th percentile for age	Drug: ZTI-01 75 mg/kg; ZTI-01 intravenous (IV); Other Names: IV fosfomycin; fosfomycin disodium; fosfomycin for injection
Experimental: ZTI-01 Cohort 3b ≥ 3 to < 6 mos of age; ZTI-01 (fosfomycin IV) 100 mg/kg (single dose) Subjects weighing within the 3rd to < 97th percentile for age	Drug: ZTI-01 100 mg/kg; ZTI-01 intravenous (IV); Other Names: IV fosfomycin; fosfomycin disodium; fosfomycin for injection
Experimental: ZTI-01 Cohort 3c ≥ 6 to < 24 mos of age; ZTI-01 (fosfomycin IV) 100 mg/kg (single dose) Subjects weighing within the 3rd to < 97th percentile for age	Drug: ZTI-01 100 mg/kg; ZTI-01 intravenous (IV); Other Names: IV fosfomycin; fosfomycin disodium; fosfomycin for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve (AUC) after a single dose of ZTI-01	By age cohort, determine the ZTI-01 pharmacokinetic area under the plasma concentration-time curve	From time end of 1-hour infusion on Day 1, up to 8-12 hours post infusion on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Treatment Emergent Adverse Events (TEAE)	Number and Incidence of TEAEs by age cohort	Baseline (start of dosing) through end of study follow-up (Day 2)
Maximum concentration (Cmax) after a single dose of ZTI-01	By age cohort, determine the ZTI-01 pharmacokinetic maximum concentration (Cmax)	From time end of 1-hour infusion on Day 1, up to 8-12 hours post infusion on Day 1

Collaborators and Investigators

• Sponsor: Nabriva Therapeutics AG
• Investigators: Study Chair: Jennifer Schranz, MD, Nabriva Therapeutics; Principal Investigator: John S Bradley, MD, Rady Children's Hospital / Department of Pediatrics, University of California, School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2018
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): January 10, 2026

Study Registration Dates

• First Submitted: October 10, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric PK
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Fosfomycin
• Other Study ID Numbers: ZTI-01-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No