Trial Outcomes & Findings for Safety of Intravenous Apramycin in Adults (NCT NCT05590728)

Last Updated: 2025-03-06

Results Overview

AUC 0-8 (ug\*h/mL) was estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF and AM concentration at one time point, so the PK parameters for ELF and AM were calculated using the geometric mean (GM) concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF and AM across all participants.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

0 h through 8 h post dose

Results posted on

2025-03-06

Participant Flow

The study population included healthy male and female adults, ages 18-45 years, inclusive, who met all eligibility criteria. Participants were enrolled between May 15, 2023 and October 16, 2023 and were recruited from the community at large.

Participants who signed the Informed Consent Form underwent screening procedures that included medical history, physical exam, clinical laboratory testing (hematology, chemistry, coagulation, urinalysis, viral serology (for HIV, HCV and HBV), and pregnancy testing. Participants who met all the inclusion criteria and none of the exclusion criteria were admitted into the clinical trial unit to confirm eligibility on Day -1 and assigned to one of the study cohorts before dosing on Day 1.

Participant milestones

Participant milestones
Measure	30 Minute BAL A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 30 minutes (+/- 5 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.	2 Hour BAL A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 2 hours (+/- 5 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.	4 Hour BAL A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 4 hours (+/- 10 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.	8 Hour BAL A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 8 hours (+/- 15 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.
Overall Study STARTED	4	4	4	4
Overall Study Started Infusion	4	4	4	4
Overall Study Completed Infusion	4	4	4	4
Overall Study Completed Bronchoscopy With BAL	4	4	4	4
Overall Study Completed All PK Blood Draws	3	4	4	4
Overall Study Completed All Plasma Urea Blood Draws	3	4	4	4
Overall Study COMPLETED	4	4	4	4
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety of Intravenous Apramycin in Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	30 Minute BAL n=4 Participants A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 30 minutes (+/- 5 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.	2 Hour BAL n=4 Participants A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 2 hours (+/- 5 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.	4 Hour BAL n=4 Participants A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 4 hours (+/- 10 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.	8 Hour BAL n=4 Participants A single 30 mg/kg apramycin dose was administered intravenously (IV) in a total volume of 30 mL over 30 minutes (+/- 5 minutes) to each participant. Bronchoscopy with bronchoalveolar lavage (BAL) performed 8 hours (+/- 15 minutes) after infusion start. Apramycin (EBL-1003): A mono-substituted 2- deoxystreptamine comprising a unique bicyclic octadiose moiety. It is a crystalline free base of the aminoglycoside apramycin. Apramycin for infusion is formulated as 150 mg free base /mL in sterile aqueous solution, pH 5.5 to 6.0 adjusted with sulfuric acid. The study product is supplied in 20 mL glass vials. Based on the participant's weight, the appropriate weight-based apramycin for infusion dose was calculated and the appropriate number of vials were removed from storage to prepare the infusion. Sterile normal saline was used to adjust the infusion volume.	Total n=16 Participants Total of all reporting groups
Age, Continuous	31.3 years STANDARD_DEVIATION 10.0 • n=5 Participants	34.0 years STANDARD_DEVIATION 3.5 • n=7 Participants	27.0 years STANDARD_DEVIATION 6.2 • n=5 Participants	30.5 years STANDARD_DEVIATION 8.8 • n=4 Participants	30.7 years STANDARD_DEVIATION 7.2 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	8 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Body Mass Index (BMI)	28.13 kg/m^2 STANDARD_DEVIATION 2.70 • n=5 Participants	27.08 kg/m^2 STANDARD_DEVIATION 2.84 • n=7 Participants	24.50 kg/m^2 STANDARD_DEVIATION 3.28 • n=5 Participants	26.78 kg/m^2 STANDARD_DEVIATION 3.10 • n=4 Participants	26.62 kg/m^2 STANDARD_DEVIATION 3.00 • n=21 Participants

PRIMARY outcome

Timeframe: 0 h through 8 h post dose

Population: The PK Analysis Subset population includes all participants who completed the lung and plasma PK parts of the trial without any protocol deviations that would likely affect the PK results and who have evaluable plasma PK and BAL PK concentration data for apramycin. All cohorts are reported jointly as all received the same dose, following the same dosing schedule.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=11 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Area Under the Concentration-time Curve From Time Zero to 8 h (AUC 0-8) of Total Apramycin in Epithelial Lining Fluid (ELF) and Alveolar Macrophage (AM) AM	131.7 ug*h/mL
Area Under the Concentration-time Curve From Time Zero to 8 h (AUC 0-8) of Total Apramycin in Epithelial Lining Fluid (ELF) and Alveolar Macrophage (AM) ELF	142.8 ug*h/mL

PRIMARY outcome

Timeframe: 0 h through 8 h post dose

AUC 0-inf (ug\*h/mL) was estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF and AM concentration at one time point, so the PK parameters for ELF and AM were calculated using the geometric mean (GM) concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF and AM across all participants.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=11 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC 0-inf) of Total Apramycin in ELF and AM ELF	197.3 ug*h/mL
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC 0-inf) of Total Apramycin in ELF and AM AM	NA ug*h/mL Phoenix WinNonlin could not calculate an estimate for this PK parameter.

PRIMARY outcome

Timeframe: 0 h though 8 h post dose

Cmax (ug/mL) was estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF and AM concentration at one time point, so the PK parameters for ELF and AM were calculated using the geometric mean (GM) concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF and AM across all participants.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=11 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Maximum Concentration (Cmax) of Total Apramycin in ELF and AM ELF	27.47 ug/mL
Maximum Concentration (Cmax) of Total Apramycin in ELF and AM AM	42.37 ug/mL

PRIMARY outcome

Timeframe: 0 h through 8 h post dose

Tmax (h) was estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF and AM concentration at one time point, so the PK parameters for ELF and AM were calculated using the geometric mean (GM) concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF and AM across all participants.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=11 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Time of Maximum Concentration (Tmax) of Total Apramycin in ELF and AM AM	8 h
Time of Maximum Concentration (Tmax) of Total Apramycin in ELF and AM ELF	0.5 h

PRIMARY outcome

Timeframe: 0 h through 8 h post dose

t1/2 (h) was estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF and AM concentration at one time point, so the PK parameters for ELF and AM were calculated using the geometric mean (GM) concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF and AM across all participants.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=11 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Terminal Elimination Half-Life (t1/2) of Total Apramycin in ELF and AM ELF	4.05 h
Terminal Elimination Half-Life (t1/2) of Total Apramycin in ELF and AM AM	NA h Phoenix WinNonlin could not calculate an estimate for this PK parameter.

PRIMARY outcome

Timeframe: 0 h through 8 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of AUC 0-8 (h\*ug/mL). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Area Under the Concentration-time Curve From Time Zero to 8 h (AUC 0-8) of Total Apramycin in Plasma	443.9 ug*h/mL Geometric Coefficient of Variation 11

PRIMARY outcome

Timeframe: 0 h through 24 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of AUC 0-24 (h\*ug/mL). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Area Under the Concentration-time Curve From Time Zero to 24 h (AUC 0-24) of Total Apramycin in Plasma	486.7 ug*h/mL Geometric Coefficient of Variation 13

PRIMARY outcome

Timeframe: 0 h through 60 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of AUC (0-last) (h\*µg/mL). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration Above the Lower Limit of Quantitation (AUC 0-last) of Total Apramycin in Plasma	490.3 ug*h/mL Geometric Coefficient of Variation 13

PRIMARY outcome

Timeframe: 0 h through 60 h post dose

Population: The Plasma PK population consists of all participants who received a complete dose of apramycin and have at least one quantifiable post-dose plasma drug concentration measured. All cohorts are reported jointly as all received the same dose, following the same dosing schedule. Four participants' concentration data did not meet the lambda-z acceptance criteria and are not included in the summary statistics.

Geometric mean (GM) and coefficient of variation as a percent (CV%) of AUC (0-Inf) (h\*µg/mL). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study. AUC 0-Inf was estimated for plasma concentration data with the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) = 0.90 and includes at least 3 timepoints after time to maximum concentration (Tmax).

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=12 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC 0-inf) of Total Apramycin in Plasma	500.3 ug*h/mL Geometric Coefficient of Variation 14

PRIMARY outcome

Timeframe: 0 h though 60 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of Cmax (ug/mL). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Maximum Concentration (Cmax) of Total Apramycin in Plasma	172.1 ug/mL Geometric Coefficient of Variation 10

PRIMARY outcome

Timeframe: 0 h through 60 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of Tmax (h). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Time of Maximum Concentration (Tmax) of Total Apramycin in Plasma	0.595 h Geometric Coefficient of Variation 32

PRIMARY outcome

Timeframe: 0 h through 60 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of t1/2 (h). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study. t1/2 was estimated for plasma concentration data with the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) = 0.90 and includes at least 3 timepoints after time to maximum concentration (Tmax).

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=12 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Terminal Elimination Half-Life (t1/2) of Total Apramycin in Plasma	19.1 h Geometric Coefficient of Variation 19

PRIMARY outcome

Timeframe: 0 h to 60 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of Vd (L/kg). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study. Vd was estimated for plasma concentration data with the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) = 0.90 and includes at least 3 timepoints after time to maximum concentration (Tmax).

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=12 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Central Volume of Distribution (Vd) of Total Apramycin in Plasma	1.64 L/kg Geometric Coefficient of Variation 22

PRIMARY outcome

Timeframe: 0 h through 60 h post dose

Geometric mean (GM) and coefficient of variation as a percent (CV%) of CLT (L/h/kg). PK parameters were estimated from the total apramycin plasma concentration-time data after a complete dose using Phoenix WinNonlin Non-compartmental analysis. Plasma concentrations were measured by a validated LC-MC/MS bioanalytical assay for plasma samples collected during the study. CLT was estimated for plasma concentration data with the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) = 0.90 and includes at least 3 timepoints after time to maximum concentration (Tmax).

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=12 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Total Clearance (CLT) of Total Apramycin in Plasma	0.0600 L/h/kg Geometric Coefficient of Variation 14

PRIMARY outcome

Timeframe: 0 h through 8 h post dose

The ratios for Cmax (ug/mL), AUC 0-8 (ug\*h/mL), and AUC 0-inf (ug\*h/mL) of ELF to plasma and AM to plasma were calculated by dividing the Cmax (ug/mL), AUC 0-8 (ug\*h/mL), and AUC 0-inf (ug\*h/mL) of ELF and AM by the Cmax (ug/mL), AUC 0-8 (ug\*h/mL), and AUC 0-inf (ug\*h/mL) of total apramycin in plasma, respectively. All PK parameters were estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF and AM concentration at one time point, so the PK parameters for ELF and AM were calculated using the GM concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF and AM across all participants. The PK parameters for total apramycin in plasma were calculated using the GM result of the total apramycin in plasma concentrations at the corresponding BAL time point.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=11 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Ratio of ELF to Plasma and AM to Plasma Apramycin Exposure Parameters Cmax, AM to Plasma	0.222 ratio of lung PK to plasma PK
Ratio of ELF to Plasma and AM to Plasma Apramycin Exposure Parameters AUC 0-8, AM to Plasma	0.299 ratio of lung PK to plasma PK
Ratio of ELF to Plasma and AM to Plasma Apramycin Exposure Parameters Cmax, ELF to Plasma	0.144 ratio of lung PK to plasma PK
Ratio of ELF to Plasma and AM to Plasma Apramycin Exposure Parameters AUC 0-inf, ELF to Plasma	0.404 ratio of lung PK to plasma PK
Ratio of ELF to Plasma and AM to Plasma Apramycin Exposure Parameters AUC 0-inf, AM to Plasma	NA ratio of lung PK to plasma PK Phoenix WinNonlin could not calculate an estimate of AUC 0-inf for AM, so a ratio could not be calculated.
Ratio of ELF to Plasma and AM to Plasma Apramycin Exposure Parameters AUC 0-8, ELF to Plasma	0.324 ratio of lung PK to plasma PK

SECONDARY outcome

Timeframe: Day 1 through Day 30

Population: The safety population includes all participants who received any amount of apramycin. All participants received the same dose of study product and are therefore reported jointly for safety outcomes.

Number of participants that experience any SAEs from Day 1 to Day 30. An AE is considered serious if, in the view of either the site principal investigator or sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Serious Adverse Events (SAEs)	0 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 30

The number of participants who experienced at least one unsolicited TEAE of any severity and relatedness. Any medical condition that was present at screening was considered a baseline finding and not reported as an AE. However, if the grade increased at any time during the trial such that it met the AE definition, it was recorded as an AE.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Treatment-emergent Adverse Events (TEAEs) Ear and labyrinth disorders	4 Participants
Frequency of Treatment-emergent Adverse Events (TEAEs) Eye disorders	1 Participants
Frequency of Treatment-emergent Adverse Events (TEAEs) General disorders and administration site conditions	1 Participants
Frequency of Treatment-emergent Adverse Events (TEAEs) Infections and infestations	1 Participants
Frequency of Treatment-emergent Adverse Events (TEAEs) Injury, poisoning and procedural complications	1 Participants
Frequency of Treatment-emergent Adverse Events (TEAEs) Investigations	5 Participants
Frequency of Treatment-emergent Adverse Events (TEAEs) Nervous system disorders	1 Participants
Frequency of Treatment-emergent Adverse Events (TEAEs) Respiratory, thoracic and mediastinal disorders	2 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 14

Abnormal physical exam findings through Day 14. Physical exams included assessment of head, eyes, ears, nose, and throat; heart, lungs, abdomen, skin, musculoskeletal system, and lymph nodes.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Abnormal Physical Exam Findings Head, Eyes, Ears, Nose, Throat (HEENT)	2 Participants
Frequency of Abnormal Physical Exam Findings Musculoskeletal	1 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 14

Abnormal vital sign findings through Day 14. Vital sign measurements include systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and oral temperature. If a vital sign finding met the threshold for an AE at baseline, subsequent vital sign results were only considered to be an AE if the grading worsened in severity.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Abnormal Vital Sign Findings Pulse - decrease	2 Participants
Frequency of Abnormal Vital Sign Findings Systolic blood pressure - decrease	1 Participants
Frequency of Abnormal Vital Sign Findings Systolic blood pressure - increase	0 Participants
Frequency of Abnormal Vital Sign Findings Diastolic blood pressure - decrease	0 Participants
Frequency of Abnormal Vital Sign Findings Diastolic blood pressure - increase	0 Participants
Frequency of Abnormal Vital Sign Findings Pulse - increase	0 Participants
Frequency of Abnormal Vital Sign Findings Respiratory rate - decrease	0 Participants
Frequency of Abnormal Vital Sign Findings Respiratory rate - increase	0 Participants
Frequency of Abnormal Vital Sign Findings Oral temperature - decrease	0 Participants
Frequency of Abnormal Vital Sign Findings Oral temperature - increase	5 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 14

Abnormal chemistry laboratory findings through Day 14. Graded chemistry laboratory measurements include sodium, potassium, glucose (fasting), blood urea nitrogen, creatinine, calcium, magnesium, carbon dioxide, albumin, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin. If a clinical chemistry laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Abnormal Chemistry Lab Measurements Alkaline phosphatase - increase	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Sodium - decrease	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Sodium - increase	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Potassium - decrease	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Potassium - increase	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Glucose - decrease	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Glucose - increase	2 Participants
Frequency of Abnormal Chemistry Lab Measurements Blood urea nitrogen - increase	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Creatinine - increase	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Calcium - decrease	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Calcium - increase	1 Participants
Frequency of Abnormal Chemistry Lab Measurements Magnesium - decrease	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Carbon dioxide - decrease	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Carbon dioxide - increase	3 Participants
Frequency of Abnormal Chemistry Lab Measurements Albumin - decrease	1 Participants
Frequency of Abnormal Chemistry Lab Measurements Total protein - decrease	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Alanine aminotransferase - increase	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Aspartate aminotransferase - increase	0 Participants
Frequency of Abnormal Chemistry Lab Measurements Total bilirubin - increase	1 Participants
Frequency of Abnormal Chemistry Lab Measurements Direct bilirubin - increase	0 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 14

Abnormal hematology laboratory findings through Day 14. Graded hematology laboratory measurements include hemoglobin, platelet count, white blood cells, neutrophils, lymphocytes, eosinophils, basophils, and monocytes. If a clinical hematology laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Abnormal Hematology Lab Measurements Hemoglobin - decrease	0 Participants
Frequency of Abnormal Hematology Lab Measurements Platelets - decrease	0 Participants
Frequency of Abnormal Hematology Lab Measurements White blood cells - decrease	2 Participants
Frequency of Abnormal Hematology Lab Measurements White blood cells - increase	2 Participants
Frequency of Abnormal Hematology Lab Measurements Neutrophils - decrease	0 Participants
Frequency of Abnormal Hematology Lab Measurements Lymphocytes - decrease	0 Participants
Frequency of Abnormal Hematology Lab Measurements Eosinophils - increase	1 Participants
Frequency of Abnormal Hematology Lab Measurements Basophils - increase	0 Participants
Frequency of Abnormal Hematology Lab Measurements Monocytes - increase	1 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 14

Abnormal coagulation laboratory findings through Day 14. Graded coagulation laboratory measurements include activated partial thromboplastin time, prothrombin time, and prothrombin international normalized ratio. If a clinical coagulation laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Abnormal Coagulation Lab Measurements Activated partial thromboplastin time - increase	3 Participants
Frequency of Abnormal Coagulation Lab Measurements Prothrombin time - increase	2 Participants
Frequency of Abnormal Coagulation Lab Measurements Prothrombin international normalized ratio - increase	2 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 14

Abnormal urinalysis laboratory findings through Day 14. Urinalysis laboratory measurements include routine dipstick testing of clean-catch urine for blood, protein, and glucose. If urine dipstick was abnormal, urine microscopy was performed. If a clinical urinalysis laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Abnormal Urinalysis Lab Measurements Protein by dipstick - increase	2 Participants
Frequency of Abnormal Urinalysis Lab Measurements Glucose by dipstick - increase	0 Participants
Frequency of Abnormal Urinalysis Lab Measurements Blood by dipstick - increase	4 Participants
Frequency of Abnormal Urinalysis Lab Measurements White blood cells by microscopy - increase	0 Participants
Frequency of Abnormal Urinalysis Lab Measurements Red blood cells by microscopy - increase	1 Participants
Frequency of Abnormal Urinalysis Lab Measurements Bacteria by microscopy - increase	1 Participants

SECONDARY outcome

Timeframe: 0 h through 24 h post dose

Changes in ECG intervals and morphological changes from baseline up to 24 hours after dosing. The graded ECG measurements include PR interval and QTcF interval.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Abnormal Changes in Electrocardiographic (ECG) Results PR interval	0 Participants
Frequency of Abnormal Changes in Electrocardiographic (ECG) Results QTcF interval	0 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 30

TEAEs related to auditory (cochlear) function tests (pure-tone audiometry and distortion product otoacoustic emissions \[DPOAEs\]) through Day 30.

Outcome measures

Outcome measures
Measure	Apramycin All Participants n=16 Participants A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Frequency of Audiology TEAEs	4 Participants

Adverse Events

Apramycin All Participants

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Apramycin All Participants n=16 participants at risk A single 30 mg/kg apramycin dose administered intravenously (IV) over 30 minutes (+/- 5 minutes).
Ear and labyrinth disorders Deafness neurosensory	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Ear and labyrinth disorders Hypoacusis	25.0% 4/16 • Number of events 5 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Ear and labyrinth disorders Tinnitus	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Eye disorders Eye pruritus	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Eye disorders Lacrimation increased	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
General disorders Pyrexia	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Infections and infestations COVID-19	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Injury, poisoning and procedural complications Skin laceration	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Blood pressure systolic decreased	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Body temperature increased	18.8% 3/16 • Number of events 4 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Heart rate decreased	12.5% 2/16 • Number of events 2 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Activated partial thromboplastin time prolonged	18.8% 3/16 • Number of events 3 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Bacterial test positive	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Bilirubin conjugated increased	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Blood albumin decreased	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Blood calcium increased	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Blood glucose increased	12.5% 2/16 • Number of events 2 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Blood urine present	25.0% 4/16 • Number of events 4 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Carbon dioxide increased	18.8% 3/16 • Number of events 3 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Eosinophil count increased	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations International normalised ratio increased	12.5% 2/16 • Number of events 2 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Monocyte count increased	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Protein urine present	12.5% 2/16 • Number of events 2 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Prothrombin time prolonged	12.5% 2/16 • Number of events 2 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations Red blood cells urine positive	6.2% 1/16 • Number of events 1 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations White blood cell count decreased	12.5% 2/16 • Number of events 2 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.
Investigations White blood cell count increased	12.5% 2/16 • Number of events 2 • All treatment emergent adverse events (TEAEs) were documented from time of study drug dosing through the time of last assessment (e.g., Day 14 +/- 3 days of clinical safety labs and ECGs) or Final Visit (Day 30 +/- 4 days). Any systemic medical condition, vital sign and ECG measurement, and clinical safety lab test value that was present on Day 1 prior to dosing was considered a baseline finding. For ear and otoacoustic testing, baseline comprises of assessment performed on Day -2. If the condition increases in severity or frequency after study product administration, it was reported as a TEAE. All participants received the same dose of study product and are therefore jointly reported for adverse events.

Additional Information

George A. Saviolakis, MD, PhD

DynPort Vaccine Company, a GDIT Company

Phone: 301-835-4101

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60