Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Florida | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Treatment Arm - 300mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tobramycin solution for inhalation 78mg dose | Drug | Inhaled tobramycin - 78mg administered every 12 hours for 14 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
A total of 27 infants were enrolled into the study protocol and underwent collection of a screening tracheal aspirate culture to determine eligibility for the entry into the phase 1 drug trial. Of these 27, 16 (59%) infants had a tracheal aspirate culture positive for an eligible Gram-negative pathogen. OF these 16, all were enrolled into the phase 1 drug trial. No parents/guardians elected to enroll their child in the untreated observational arm prior to completion of all dose levels.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Arm - 78mg | 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. Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days. |
| FG001 | Treatment Arm - 150mg | 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. Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days. |
| FG002 | Treatment Arm - 216mg | 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. Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days. |
| FG003 | Treatment Arm - 300mg | 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. Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days. |
| FG004 | Observational Arm | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
A total of 27 infants were enrolled into the study protocol and underwent collection of a screening tracheal aspirate culture to determine eligibility for the entry into the phase 1 drug trial. Of these 27, 16 (59%) infants had a tracheal aspirate culture positive for an eligible Gram-negative pathogen. OF these 16, all were enrolled into the phase 1 drug trial. No parents/guardians elected to enroll their child in the untreated observational arm prior to completion of all dose levels.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Arm - 78mg | 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. Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome. | Posted | Count of Participants | Participants | Any time during the 14-day trial |
|
During the 14 day drug trial and continuing until hospital discharge
Adverse event data was not captured on infants who were screened but not enrolled into the drug trial.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Arm - 78mg | 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. Tobramycin solution for inhalation 78mg dose: Inhaled tobramycin - 78mg administered every 12 hours for 14 days. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Desturation episode outside of study drug administration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Episodes of desaturation (SpO2<80%) lasting longer than 30 seconds that is possibly/probably related to study drug administration |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Erik Jensen, MD, MSCE | Stanford University School of Medicine | 267-648-2720 | jensene@stanford.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 20, 2023 | Nov 21, 2024 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D001997 | Bronchopulmonary Dysplasia |
| ID | Term |
|---|---|
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001239 | Inhalation |
| ID | Term |
|---|---|
| D015656 | Respiratory Mechanics |
| D012119 | Respiration |
| D012143 | Respiratory Physiological Phenomena |
| D002943 | Circulatory and Respiratory Physiological Phenomena |
Not provided
Not provided
3+3 dose escalation trial.
Not provided
Not provided
Not provided
Not provided
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.
|
| 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. |
| Tobramycin solution for inhalation 150mg dose | Drug | Inhaled tobramycin - 150mg administered every 12 hours for 14 days. |
|
| Tobramycin solution for inhalation 216mg dose | Drug | Inhaled tobramycin - 216mg administered every 12 hours for 14 days. |
|
| Tobramycin solution for inhalation 300mg dose | Drug | Inhaled tobramycin - 300mg administered every 12 hours for 14 days. |
|
| 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 |
| New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization | up to 1 year of age |
| Change in Tracheal Aspirate Pathogenic Bacterial Colony Forming Unit (CFU) Counts Measured by Quantitative Culture | During the 14-day trial |
| Change in the Fraction of Inspired Oxygen (FiO2), Ventilator Mean Airway Pressure (MAP), and Respiratory Severity Score (MAP x FiO2) | During the 14-day trial |
| Change in Intermittent Hypoxemia (SpO2<80% Lasting >/=10s), Prolonged Hypoxemia (SpO2<80% Lasting >1min), and Daily Proportion of Time in Hypoxemia | During the 14-day trial |
| Change in Tracheal Aspirate Cytokine Levels, Neutrophil to Total WBC Ratio, and Patterns in the Airway Microbiome | During the 14-day trial |
| Change in Dynamic Lung Compliance, Airway Resistance, Peak Expiratory Flow, and Carbon Dioxide (CO2) Elimination | During the 14-day trial |
| Adverse Event |
|
| BG001 | Treatment Arm - 150mg | 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. Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days. |
| BG002 | Treatment Arm - 216mg | 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. Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days. |
| BG003 | Treatment Arm - 300mg | 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. Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days. |
| BG004 | Observational Arm | 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. |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Treatment Arm - 150mg | 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. Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days. |
| OG002 | Treatment Arm - 216mg | 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. Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days. |
| OG003 | Treatment Arm - 300mg | 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. Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days. |
| OG004 | Observational Arm | 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. |
|
|
| Secondary | New Onset or Worsened Coughing Associated With a Change in Respiratory Status (SpO2 <80% for >10 Seconds; Need for Increase in FiO2 by >20%) | No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome. | Posted | Count of Participants | Participants | Any time during the 14-day trial |
|
|
|
| Secondary | Obstruction of the Endotracheal Tube Requiring Tube Replacement | No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome. | Posted | Count of Participants | Participants | Any time during the 14-day trial |
|
|
|
| Secondary | Unplanned Tracheal Extubation | No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome. | Posted | Count of Participants | Participants | Any time during the 14-day trial |
|
|
|
| Secondary | Desaturation (SpO2 <80% for >10 Seconds) During Administration of Inhaled Tobramycin | No infants were enrolled into the observational arm. Infants who were screened but not eligible did not receive study drug. | Posted | Count of Participants | Participants | Any time during the 14 day trial |
|
|
|
| Secondary | Pre-discharge Failed Audiology Examination | 14 of the 16 phase 1 trial participants were assessed for failed audiology examination. The remaining two died prior to testing. | Posted | Count of Participants | Participants | up to 1 year of age |
|
|
|
| Secondary | New Intra-patient Microbial Resistance to Tobramycin During the Primary Hospitalization | No infants were enrolled into the observational arm. 1 of the 16 enrolled infants (treatment arm - 78mg) was withdrawn early from the trial by the medical team and was not assessed for this outcome. | Posted | Count of Participants | Participants | up to 1 year of age |
|
|
|
| Secondary | Change in Tracheal Aspirate Pathogenic Bacterial Colony Forming Unit (CFU) Counts Measured by Quantitative Culture | CFU counts were not measured by the microbiology lab on tracheal aspirate samples; only presence/absence of pathogens was recorded owing to variable consistency of sputum samples. No infants were enrolled into the observational arm. | Posted | During the 14-day trial |
|
|
| Secondary | Change in the Fraction of Inspired Oxygen (FiO2), Ventilator Mean Airway Pressure (MAP), and Respiratory Severity Score (MAP x FiO2) | Not Posted | Dec 2025 | During the 14-day trial | Participants |
| Secondary | Change in Intermittent Hypoxemia (SpO2<80% Lasting >/=10s), Prolonged Hypoxemia (SpO2<80% Lasting >1min), and Daily Proportion of Time in Hypoxemia | Not Posted | Dec 2025 | During the 14-day trial | Participants |
| Secondary | Change in Tracheal Aspirate Cytokine Levels, Neutrophil to Total WBC Ratio, and Patterns in the Airway Microbiome | Not Posted | Dec 2025 | During the 14-day trial | Participants |
| Secondary | Change in Dynamic Lung Compliance, Airway Resistance, Peak Expiratory Flow, and Carbon Dioxide (CO2) Elimination | Not Posted | Dec 2025 | During the 14-day trial | Participants |
| 2 |
| 4 |
| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | Treatment Arm - 150mg | 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. Tobramycin solution for inhalation 150mg dose: Inhaled tobramycin - 150mg administered every 12 hours for 14 days. | 0 | 3 | 0 | 3 | 1 | 3 |
| EG002 | Treatment Arm - 216mg | 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. Tobramycin solution for inhalation 216mg dose: Inhaled tobramycin - 216mg administered every 12 hours for 14 days. | 1 | 3 | 0 | 3 | 1 | 3 |
| EG003 | Treatment Arm - 300mg | 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. Tobramycin solution for inhalation 300mg dose: Inhaled tobramycin - 300mg administered every 12 hours for 14 days. | 1 | 6 | 0 | 6 | 1 | 6 |
| EG004 | Observational Arm | 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. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG005 | Screened But Not Eligible | Enrolled infants who did not have evidence of a Gram-negative bacteria present on a prospective tracheal aspirate culture obtained for this trial and thus were not eligible to receive study drug. | 0 | 0 | 0 | 0 | 0 | 0 |
|
Not provided
Not provided
| D007235 |
| Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |