Safety of Intravenous Apramycin in Adults

Inclusion Criteria

• Subject reads and signs the Informed Consent Form (ICF) and agree to have bronchoscopy with bronchoalveolar lavage under sedation or light anesthesia and comply with study procedures.
• Healthy male or non-pregnant, non-lactating female subjects 18 to 45 years of age (both inclusive) at the time of dosing.

*Note 1: Determined by medical history (MH), medication use, physical examination (PE), and vital signs, clinical laboratory tests and 12-lead ECG within reference ranges at Screening and Day-2. (See Sections 8.1 and 8.2; and Appendix B, Table 2, Table 3 and Table 4 and the study-specific MOP.)

Exceptions to BP, HR and laboratory test values being with normal ranges are:

• Abnormal HR and BP on first measurement may be repeated twice more with the subject resting between measurements for at least 5 min according to Section 8.1.6.
• Subjects with baseline HR >/= 45 to 50 bpm may be accepted if otherwise healthy adults with known history of asymptomatic bradycardia.
• Subjects with baseline SBP up to 140 mmHg and DBP up to 90 mmHg may be accepted if otherwise healthy.
• A laboratory value that is Grade 1 will be allowed if not considered to be clinically significant by the investigator, with the exception of ALT, AST, AP, BUN, urine protein, serum creatinine or estimated glomerular filtration rate (eGFR) /=1 year of spontaneous amenorrhea and a FSH level >40 IU/L), or permanently surgically sterilized.
• Note 2: Highly effective contraceptive methods include: (a) surgical sterilization methods, such as tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful tubal obliteration (e.g., Essure(R)) with documented radiological confirmation test at least 90 days after the procedure, or (b) long-acting reversible contraception, such as progestin-releasing subdermal implants, copper intrauterine devices (IUDs), levonorgestrel-releasing IUDs.
• Note 3: A subject who is not sexually active and abstains from sexual intercourse can be enrolled and abstinence documented.
• Males, including vasectomized men, having sexual intercourse with women of childbearing potential must agree to consistent use of condoms from IMP administration through at least 30 days after dosing, and must also agree to not donate sperm during this same time period.

*Note: A subject who is not sexually active and abstains from sexual intercourse can be enrolled and abstinence documented.

• BMI 18.0 to 32.0 kg/m^2 (inclusive) and body weight not less than 50 kg.
• Subjects with normal hearing, i.e., symmetric hearing with air conduction thresholds no worse than 20 dB hearing loss for the frequencies 0.5-1-2-4-6-8 kHz bilaterally.
• Normal (reproducibility 70% or better) of distortion product otoacoustic emissions (DPOAEs).

*Note: Absence of DPOAEs at no more than two consecutive or non-consecutive DPOAEs in each ear is acceptable.

• Normal otoscopic findings in the ears, normal tympanic membrane mobility and stapedial reflex present.
• From the signing of the informed consent until the last follow-up visit, subjects must be willing to avoid exposure to loud music or noise.

*Note: Noise avoidance to include continuous usage of earpieces at high volume, attending loud concerts or dance events, or using firearms or attending fireworks.

• Normal lung function with Forced Expiratory Volume in the first second (FEV1) predicted >/= 80% and FEV1/Forced Vital Capacity (FVC) > 70%.
• Subjects must be willing to avoid excessive physical exercise within 48 h prior to dosing until discharge from the CTU on Day 3, and 24 h before each follow-up visit (Day 14 +/- 3 days and Day 30 +/- 4 days).
• No history of acute febrile or infectious illness for at least 7 days prior to the administration of the IMP.
• No history of lower respiratory tract infection within 4 weeks prior to screening.
• Have adequate venous access for infusion and blood draws.

Exclusion Criteria

All must be answered NO for the subject to b