Inhaled Tobramycin in BPD

NCT04560179 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 19-016800
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, phase 1, sequential dose escalation trial seeking to establish preliminary tolerability, efficacy, and pharmacokinetic data for up to 4 different doses of inhaled tobramycin administered to very preterm infants with BPD who are receiving invasive mechanical ventilation and have a pathogenic Gram-negative organism detected by tracheal aspirate culture.

Conditions

Bronchopulmonary Dysplasia

Outcome Measures

Primary Outcomes (1)

• Elevated Serum Tobramycin Trough or Creatinine or Severe Adverse Event

  Trough serum tobramycin level (measured 11 hours after the administered dose) ≥1mcg/mL; increase in serum creatinine level by ≥0.3mg/dL above pre-trial baseline; increase in serum creatinine level \>1.5-fold above pre-trial baseline; urine output \<0.5mL/kg/hr for 12 consecutive hours; or any serious adverse event possibly attributable to the study drug

  Any time during the 14-day trial

Secondary Outcomes (11)

• New Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%)

  Any time during the 14-day trial

• Obstruction of the Endotracheal Tube Requiring Tube Replacement

  Any time during the 14-day trial

• Unplanned Tracheal Extubation

  Any time during the 14-day trial

• Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin

  Any time during the 14 day trial

• Pre-discharge Failed Audiology Examination

  up to 1 year of age

Study Arms (5)

Treatment Arm - 78mg

EXPERIMENTAL

The phase 1 trial will begin with a dose of 78mg. All treatment arms will administer study drug every 12 hours for up to 14 days (28 doses). Up to 6 infants in this arm will receive the 78mg dose of tobramycin solution for inhalation administered via vibrating mesh nebulizer. During the trial, infants in each treatment arm will undergo blood and tracheal aspirate sampling and respiratory mechanics measurements at pre-specified time points to assess dose safety and potential efficacy. Continuous pulse oximetry monitoring for the duration of the trial will also occur. Clinical data will also be recorded daily throughout the trial in all participants.

Drug: Tobramycin solution for inhalation 78mg dose

Treatment Arm - 150mg

EXPERIMENTAL

If tolerability is demonstrated in the 78mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.

Drug: Tobramycin solution for inhalation 150mg dose

Treatment Arm - 216mg

EXPERIMENTAL

If tolerability is demonstrated in the 150mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.

Drug: Tobramycin solution for inhalation 216mg dose

Treatment Arm - 300mg

EXPERIMENTAL

If tolerability is demonstrated in the 216mg treatment arm following the 3+3 trial design, up to 6 infants will then be enrolled and receive 150mg of tobramycin solution for inhalation every 12 hours. The same monitoring procedures will be performed in this treatment arm as in the prior.

Drug: Tobramycin solution for inhalation 300mg dose

Observational Arm

NO INTERVENTION

Enrolled infants who are eligible to participate in the phase-1 trial may be enrolled in an untreated observational cohort at parental discretion. This cohort will undergo collection of clinical and respiratory mechanics data for 14 days after enrollment but will not receive the study drug.

Interventions

Tobramycin solution for inhalation 78mg dose DRUG

Inhaled tobramycin - 78mg administered every 12 hours for 14 days.

Treatment Arm - 78mg

Tobramycin solution for inhalation 150mg dose DRUG

Inhaled tobramycin - 150mg administered every 12 hours for 14 days.

Treatment Arm - 150mg

Tobramycin solution for inhalation 216mg dose DRUG

Inhaled tobramycin - 216mg administered every 12 hours for 14 days.

Treatment Arm - 216mg

Tobramycin solution for inhalation 300mg dose DRUG

Inhaled tobramycin - 300mg administered every 12 hours for 14 days.

Treatment Arm - 300mg

Eligibility Criteria

• Age: 4 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female infants born \<32 weeks' gestation
• Diagnosed with BPD (use of supplemental oxygen or respiratory support at 36 weeks postmenstrual age )
• Postmenstrual age ≥36 weeks at study enrollment
• Treatment with invasive mechanical ventilation at enrollment without planned tracheal extubation within 7 days after enrollment
• Tracheal aspirate culture positive for one of the following pathogenic GNR bacteria within 7 days prior to enrollment: Pseudomonas aeruginosa, Klebsiella species, Enterobacter species, Stenotrophomonas maltophilia, Escherichia coli, Acinetobacter baumannii, or Serratia marcescens
• Parental/guardian permission (informed consent).

You may not qualify if:

• Serum creatinine \>0.4mg/dL within 14 days prior to enrollment
• Congenital or acquired disease of the kidney or renal collecting system that adversely affects renal function
• Congenital or acquired hepatobiliary disease that adversely affects liver function
• Treatment with a systemic antibiotic within 7 days prior to enrollment
• Treatment with a nephrotoxic medication, excluding diuretics, within 48 hours prior to enrollment
• Treatment with a neuromuscular blocker within 48 hours prior to enrollment
• Known intolerance to aminoglycoside antibiotics
• Current treatment with high frequency or other oscillating mechanical ventilation
• Presence of a cancer diagnosis
• Maternal family history of early onset hearing loss defined as the need for an assistive hearing device prescribed before 30 years of age
• Endotracheal tube leak \>20%.
• Any prior use of an investigational drug \[as part of an FDA approved Investigational New Drug (IND) protocol\].
• A subject who, in the judgement of the Investigator, is not an appropriate candidate for this research study.

Sponsors & Collaborators

• Erik Allen Jensen: lead
• University of Florida: collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Erik Jensen, MD, MSCE
• Organization: Stanford University School of Medicine

jensene@stanford.edu

267-648-2720

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics / Attending Neonatologist

Model Details: 3+3 dose escalation trial.

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 23, 2020
• Study Start: March 22, 2022
• Primary Completion: December 31, 2023
• Study Completion: May 17, 2024
• Last Updated: January 31, 2025
• Results First Posted: January 31, 2025

Record last verified: 2024-12

Locations

US (1)