Inhaled Tobramycin in BPD

Erik Allen Jensen

Status and phase: Completed; Phase 1

Conditions: Bronchopulmonary Dysplasia

Treatments: Drug: Tobramycin solution for inhalation 150mg dose; Drug: Tobramycin solution for inhalation 78mg dose; Drug: Tobramycin solution for inhalation 300mg dose; Drug: Tobramycin solution for inhalation 216mg dose

Study type: Interventional

Funder types: Other

Identifiers

NCT04560179

19-016800

Details and patient eligibility

About

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.

Enrollment: 27 patients

Sex: All

Ages: 4+ weeks old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female infants born <32 weeks' gestation
2. Diagnosed with BPD (use of supplemental oxygen or respiratory support at 36 weeks postmenstrual age )
3. Postmenstrual age ≥36 weeks at study enrollment
4. Treatment with invasive mechanical ventilation at enrollment without planned tracheal extubation within 7 days after enrollment
5. 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
6. Parental/guardian permission (informed consent).

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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27 participants in 5 patient groups

Treatment Arm - 78mg

Experimental group

Description:

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.

Treatment:

Drug: Tobramycin solution for inhalation 78mg dose

Treatment Arm - 150mg

Experimental group

Description:

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.

Treatment:

Drug: Tobramycin solution for inhalation 150mg dose

Treatment Arm - 216mg

Experimental group

Description:

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.

Treatment:

Drug: Tobramycin solution for inhalation 216mg dose

Treatment Arm - 300mg

Experimental group

Description:

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.

Treatment:

Drug: Tobramycin solution for inhalation 300mg dose

Observational Arm

No Intervention group

Description:

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.