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A Safety and PK Study of IV Eravacycline

Phase 1
Completed
Conditions
Bacterial Infections
Interventions
Registration Number
NCT03696550
Lead Sponsor
Tetraphase Pharmaceuticals, Inc.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
19
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 1Eravacycline (TP-434)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
Cohort 2Eravacycline (TP-434)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
Primary Outcome Measures
NameTimeMethod
Assess the Pharmacokinetics (PK) parameters for CL, systemic clearanceScreening (-2 to 1) to Day 7

CL, systemic clearance

Assess the Pharmacokinetics (PK) parameters for Vd, volume of distributionScreening (-2 to 1) to Day 7

Vd, volume of distribution

Assess the Pharmacokinetics (PK) parameters for Cmax, maximum observed plasma concentrationScreening (-2 to 1) to Day 7

Cmax, maximum observed plasma concentration

Assess the Pharmacokinetics (PK) parameters for AUC0-t, area under the plasma concentration-time curveScreening (-2 to 1) to Day 7

AUC0-t, area under the plasma concentration

Assess the Pharmacokinetics (PK) parameters for AUC0-24, area under the plasma concentration-time curve from time 0 to 24 hours after doseScreening (-2 to 1) to Day 7

AUC0-24, area under the plasma concentration-time curve from time 0 to 24 hours after dose

Assess the Pharmacokinetics (PK) parameters for t1/2, elimination half-lifeScreening (-2 to 1) to Day 7

t1/2, elimination half-life

Assess the Pharmacokinetics (PK) parameters for Clast,, last observed plasma concentrationScreening (-2 to 1) to Day 7

Clast, last observed plasma concentration

Assess the Pharmacokinetics (PK) parameters for AUC0-inf, area under the plasma concentration-time curve extrapolated to infinite timeScreening (-2 to 1) to Day 7

AUC0-inf, area under the plasma concentration-time curve extrapolated to infinite time

Secondary Outcome Measures
NameTimeMethod
Adverse EventsFrom the time of signing the informed consent form to Day 7

Assess Adverse Events to assess safety and tolerability

Vital Signs including blood pressureScreening (-2 to 1) to Day 7

Changes in blood pressure

Vital Signs including respiratory rateScreening (-2 to 1) to Day 7

Changes in respiratory rate

Vital Signs including body temperatureScreening (-2 to 1) to Day 7

Changes in body temperature

A Directed Physical examination including chest/respiratoryScreening (-2 to 1) to Day 7.

Changes in Physical examination findings including chest/respiratory

A Directed Physical examination including heart/cardiovascularScreening (-2 to 1) to Day 7.

Changes in Physical examination findings including heart/cardiovascular

Vital Signs including heart rateScreening (-2 to 1) to Day 7

Changes in heart rate

Safety laboratory results including clinical chemistryScreening (-2 to 1) to Day 7

Changes in Clinical laboratory tests including clinical chemistry

Safety laboratory tests including hematologyScreening (-2 to 1) to Day 7

Changes in Clinical laboratory tests including hematology

Trial Locations

Locations (7)

Louisiana State University Health Sciences Center

🇺🇸

Shreveport, Louisiana, United States

University Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital

🇺🇸

Cleveland, Ohio, United States

Ronald Reagan University of California Los Angeles Medical Center

🇺🇸

Los Angeles, California, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Lurie Children's Hospital

🇺🇸

Chicago, Illinois, United States

West Virginia University Hospital

🇺🇸

Morgantown, West Virginia, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

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