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

NCT03709914 | Unknown Phase 1 FDA Drug

• 1 other identifier: ZTI-01-100
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

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).

Conditions

Pediatric ALL

Keywords

Pediatric PK

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Safety: Treatment Emergent Adverse Events (TEAE)

  Baseline (start of dosing) through end of study follow-up (Day 2)

• Maximum concentration (Cmax) after a single dose of ZTI-01

  From time end of 1-hour infusion on Day 1, up to 8-12 hours post infusion on Day 1

Study Arms (5)

ZTI-01 Cohort 1 ≥ 6 to <12 years of age

EXPERIMENTAL

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 Cohort 2 ≥ 2 to <6 years of age

EXPERIMENTAL

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 Cohort 3a Birth to < 3 mos of age

EXPERIMENTAL

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 Cohort 3b ≥ 3 to < 6 mos of age

EXPERIMENTAL

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 Cohort 3c ≥ 6 to < 24 mos of age

EXPERIMENTAL

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

Interventions

ZTI-01 100 mg/kg DRUG

ZTI-01 intravenous (IV)

Also known as: IV fosfomycin, fosfomycin disodium, fosfomycin for injection

ZTI-01 Cohort 1 ≥ 6 to <12 years of age; ZTI-01 Cohort 2 ≥ 2 to <6 years of age; ZTI-01 Cohort 3b ≥ 3 to < 6 mos of age; ZTI-01 Cohort 3c ≥ 6 to < 24 mos of age

ZTI-01 75 mg/kg DRUG

ZTI-01 intravenous (IV)

Also known as: IV fosfomycin, fosfomycin disodium, fosfomycin for injection

ZTI-01 Cohort 3a Birth to < 3 mos of age

Eligibility Criteria

• Age: Up to 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nabriva Therapeutics AG: lead

Study Sites (5)

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

RECRUITING

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

RECRUITING

University of New Mexico Hospital

Albuquerque, New Mexico, 87106, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Fosfomycin; Injections

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• John S Bradley, MD

  Rady Children's Hospital / Department of Pediatrics, University of California, School of Medicine

  PRINCIPAL INVESTIGATOR

• Jennifer Schranz, MD

  Nabriva Therapeutics

  STUDY CHAIR

Central Study Contacts

Steve Gelone

CONTACT

6108166641; Steve.Gelone@nabriva.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Subjects \<12 years of age, are assigned by age to one of five age based cohorts. Study is open label and not masked.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: multiple-center, non-comparative, open-label, PK study

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: October 17, 2018
• Study Start: May 24, 2018
• Primary Completion: December 31, 2025
• Study Completion: January 10, 2026
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)