A Safety and PK Study of IV Eravacycline

A Phase 1, Open-label, Multicenter Study to Determine the Pharmacokinetics and Safety of Intravenous Eravacycline in Children With Suspected or Confirmed Bacterial Infection

This is a Phase 1, open-label, multi-center study to determine the pharmacokinetics and safety of intravenous Eravacycline in Children with Suspected or Confirmed Bacterial Infection. Male and Female subjects from 8 to <18 years of age who fulfill the inclusion/exclusion criteria will be enrolled in this study.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: Eravacycline (TP-434)

Detailed Description

This is a Phase 1, open-label, single dose study to evaluate PK, safety, and tolerability of IV eravacycline in children with suspected or confirmed bacterial infection who are receiving systemic antibiotic therapy, other than eravacycline. The study design will allow for evaluation of PK and safety of IV eravacycline in a pediatric population at exposures predicted to be comparable to those already studied in adults. The study design is depicted in Figure 1.

Two cohorts defined by age group will be enrolled simultaneously:

• Cohort 1: 12 to <18 years of age (adolescents)
• Cohort 2: 8 to <12 years of age (younger children) Eravacycline will be administered as a single IV dose using the optimum dosage determined from PK-PD modeling and model-based simulations of phase 1, 2, and 3 adult data. Blood samples will be collected for PK analysis at predetermined timepoints.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Ronald Reagan University of California Los Angeles Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female from 8 to <18 years of age on the day informed consent (and assent, if applicable) is obtained
2. Written informed consent from parent(s) or other legally authorized representative(s) and informed assent from subject (if age appropriate according to local requirements)
3. Hospitalized, in stable condition, and receiving or plan to receive within 24 hours systemic antibiotic therapy, other than eravacycline, for a suspected or confirmed bacterial infection
4. Likely to survive the current illness
5. In the Investigator's opinion, the subject will require hospitalization for at least 24 hours following administration of the study drug
6. The subject appears to have sufficient intravascular access (peripheral or central) to receive study drug

Exclusion Criteria:

1. Evidence or history of a clinically significant medical condition that may, in the assessment of the Investigator, impair study participation or pose a significant safety risk or diminish the subject's ability to undergo all study procedures and assessments
2. Received an investigational product and/or device within 30 days prior to study drug administration or is currently enrolled in any other clinical study involving an investigational product or any other type of medical treatment judged by the Investigator, in consultation with the Medical Monitor, not to be scientifically or medically compatible with this study
3. History of hypersensitivity to tetracycline antibiotics
4. Prior dosing in this protocol
5. Unlikely to survive at least 48 hours following administration of study drug
6. Unable or unwilling, in the judgment of the Investigator, to comply with the protocol
7. Subject is a child of an employee of the Investigator or study center who has direct involvement in the proposed study or other studies under the direction of the same Investigator or study center, or an immediate family member of the employee or the Investigator, defined as a spouse, parent, child, or sibling, whether biological or legally adopted
8. Breastfeeding females
9. Females of childbearing potential [those with menarche and/or thelarche (beginning of breast development)] and sexually active males who are unwilling or unable to use an acceptable method of contraception
10. Positive pregnancy test in females of childbearing potential
11. Any other circumstance that, in the opinion of the Investigator, would preclude subject participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Eravacycline (TP-434) intravenous formulation Eravacycline will be administered as a single 60 minute IV infusion according to age. Age group (years) Dose (mg/kg) 12 to <18 (Cohort 1) 1.50	Drug: Eravacycline (TP-434); Subjects will be stratified by age into 2 cohorts, as follows: Cohort 1: from 12 to <18 years of age (N=8); Cohort 2: from 8 to <12 years of age (N=12 or at least 60% of subjects); Other Names: Trade name: Xerava™
Experimental: Cohort 2; Eravacycline will be administered as a single 60 minute IV infusion according to age. Age group (years) Dose (mg/kg) 8 to <12 (Cohort 2) 1.75	Drug: Eravacycline (TP-434); Subjects will be stratified by age into 2 cohorts, as follows: Cohort 1: from 12 to <18 years of age (N=8); Cohort 2: from 8 to <12 years of age (N=12 or at least 60% of subjects); Other Names: Trade name: Xerava™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Pharmacokinetics (PK) parameters for Cmax, maximum observed plasma concentration	Cmax, maximum observed plasma concentration	Screening (-2 to 1) to Day 7
Assess the Pharmacokinetics (PK) parameters for AUC0-t, area under the plasma concentration-time curve	AUC0-t, area under the plasma concentration	Screening (-2 to 1) to Day 7
Assess the Pharmacokinetics (PK) parameters for AUC0-inf, area under the plasma concentration-time curve extrapolated to infinite time	AUC0-inf, area under the plasma concentration-time curve extrapolated to infinite time	Screening (-2 to 1) to Day 7
Assess the Pharmacokinetics (PK) parameters for AUC0-24, area under the plasma concentration-time curve from time 0 to 24 hours after dose	AUC0-24, area under the plasma concentration-time curve from time 0 to 24 hours after dose	Screening (-2 to 1) to Day 7
Assess the Pharmacokinetics (PK) parameters for t1/2, elimination half-life	t1/2, elimination half-life	Screening (-2 to 1) to Day 7
Assess the Pharmacokinetics (PK) parameters for Clast,, last observed plasma concentration	Clast, last observed plasma concentration	Screening (-2 to 1) to Day 7
Assess the Pharmacokinetics (PK) parameters for CL, systemic clearance	CL, systemic clearance	Screening (-2 to 1) to Day 7
Assess the Pharmacokinetics (PK) parameters for Vd, volume of distribution	Vd, volume of distribution	Screening (-2 to 1) to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Assess Adverse Events to assess safety and tolerability	From the time of signing the informed consent form to Day 7
A Directed Physical examination including chest/respiratory	Changes in Physical examination findings including chest/respiratory	Screening (-2 to 1) to Day 7.
A Directed Physical examination including heart/cardiovascular	Changes in Physical examination findings including heart/cardiovascular	Screening (-2 to 1) to Day 7.
Vital Signs including blood pressure	Changes in blood pressure	Screening (-2 to 1) to Day 7
Vital Signs including heart rate	Changes in heart rate	Screening (-2 to 1) to Day 7
Vital Signs including respiratory rate	Changes in respiratory rate	Screening (-2 to 1) to Day 7
Vital Signs including body temperature	Changes in body temperature	Screening (-2 to 1) to Day 7
Safety laboratory results including clinical chemistry	Changes in Clinical laboratory tests including clinical chemistry	Screening (-2 to 1) to Day 7
Safety laboratory tests including hematology	Changes in Clinical laboratory tests including hematology	Screening (-2 to 1) to Day 7

Collaborators and Investigators

• Sponsor: Tetraphase Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2018
• Primary Completion (Actual): March 14, 2021
• Study Completion (Actual): March 19, 2021

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: October 2, 2018
• First Posted (Actual): October 4, 2018

Study Record Updates

• Last Update Posted (Actual): December 3, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Infections; Bacterial Infections
• Other Study ID Numbers: TP-434-028

Drug and device information, study documents

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