Phase 1 Study of ELX-02 in Healthy Adult Subjects

Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

• Be able and willing to provide written Informed Consent indicating that the subject has been informed of all pertinent aspects of the study.
• Healthy female subjects and male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive.

Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate measurement, 12-lead electrocardiogram (ECG), and clinical laboratory tests.

• Female subjects of non-childbearing potential must meet at least one of the following criteria:
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; post-menopausal status will be confirmed by a serum follicle-stimulating hormone level;
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential and may be enrolled if they have negative pregnancy tests at screening and admission day and agree to use a highly effective method of contraception for 14 days before first study drug administration and 28 days after last study drug administration. Female subjects of childbearing potential must agree to undergo repeated pregnancy tests.
• Male subjects must be willing to use an effective method of contraception. They must agree to use a condom consistently and correctly, during the course of the study until 28 days after last study drug administration.
• Not using any prescription medication and dietary supplements within 30 days or 5 half lives (whichever is longer) prior to the first study drug administration, except for contraceptives - nor be taking any over-the-counter (OTC) herbal or medicinal products. As an exception, acetaminophen/paracetamol may be used at doses of ≤2 g/day.
• Non-smoking and no use of any tobacco or nicotine products (by declaration) for a period of at least 6 months prior to screening visit.
• Be on no medication with potential to impair renal function (e.g., non steroidal anti inflammatory [NSAID]s) or with ototoxic potential (e.g., quinine, salicylates, aminoglycosides).
• Normal renal function (glomular filtration rate >60 mL/min) based on creatinine plasma concentration and the Modification of Diet in Renal Disease (MDRD) equation for estimated glomular filtration rate. Subjects with lower MDRD clearance can be included on the condition that they have a normal 24h creatinine clearance (determined by a 24h urine collection).
• Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) serology tests at screening.
• No history of alcohol or DOA. Negative urine test for DOA and alcohol breath test at screening and Day -1.
• No personal history (or current) or hereditary hearing loss, persistent tinnitus, persistent vertigo, persistent imbalance and persistent unsteadiness.
• Body Mass Index (BMI) of 19.0 to 30.0 kg/m2 (inclusive); and a total body weight >50.0 kg (110 lbs) and 55 dB and/or inter-ear difference in any frequency of >20 dB.

Dizziness Handicap Inventory (DHI)-H score>16. Tinnitus Handicap Inventory (THI)-H score >14.

• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of screening.
• Screening supine BP ≥ 140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic), following at least 5 min of supine rest. If BP is ≥ 140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to deter