A Phase I, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Apramycin Administered Intravenously in Healthy Adults.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Type and incidence of TEAEs related to auditory and vestibular function tests.
研究概览
简要总结
This is a first-in-human study to assess the safety, tolerability and pharmacokinetics of escalating single doses of apramycin. This trial will be conducted as a single ascending dose trial in up to 5 sequential dose cohorts (group-comparison). Each cohort will consist of 8 healthy subjects, 6 will receive apramycin and 2 placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects of non-childbearing potential, 18-45 years of age (both inclusive), body mass index 18.0 - 29.9 kg/m2 (inclusive) and body weight from 50 to 100 kg (inclusive).
- •Glomerular filtration rate (GFR) ≥ 90 mL/min /1.73 m
- •Subjects with systemic hearing, with air conduction thresholds no worse than 20 decibels (dB) hearing loss for the frequencies 0.5-1-2-4-6-8 kilohertz (kHz) bilaterally and, no threshold asymmetry ≥ 20 dB at any frequency, normal (reproducibility 70% or better) transient evoked otoacoustic emissions (TEOAE).
- •From the signing of the informed consent until the last follow-up visit, subjects must be willing to avoid exposure to loud noise and Subjects must be willing to avoid excessive physical exercise within 48 h prior to dosing.
- •Normal blood pressure and pulse rate, ECG recording without clinically significant abnormalities.
- •Thyroid-stimulating hormone, free triiodothyronine and free thyroxine within the reference ranges.
- •Having had no febrile or infectious illness for at least 7 days prior to the first administration of the Investigational medicinal product (IMP) of the study.
- •Normal microscopic findings in the ears, normal tympanic membrane mobility and stapedial reflex present.
排除标准
- •Vegetarian or vegan.
- •Demonstrating excess in xanthine consumption.
- •More than low-risk alcohol consumption (men: ≥24 g of pure alcohol regularly per day; women: ≥12 g of pure alcohol regularly per day).
- •Any history of alcohol or drug abuse or a positive urine drug screen test. Positive alcohol breath test.
- •Consumption of xanthine-containing food or beverages within 48 h before dosing.
- •Smokers smoking more than 10 cigarettes or equivalent per day.
- •Exposure to loud noise within 3 days prior to drug administration.
- •Taking any medication on a regular basis, with the exception of solitary doses of up to 1000 mg paracetamol.
- •Use of any investigational drug product within 30 days or 5 half-lives before screening.
- •Use of aminoglycosides or other antibiotics within 3 months prior to screening.
- •Use of neuromuscular blocking agents within 1 week or 5 half-lives prior to screening.
- •Use of potentially nephrotoxic medication 2 weeks prior to the drug administration.
- •Any history of drug hypersensitivity, asthma, urticaria or other severe allergic diathesis as well as hay fever with ongoing symptoms.
- •Any history of hypersensitivity to aminoglycosides.
- •Any history or signs of acute, chronic or recurrent metabolic, renal, hepatic, pulmonary, gastrointestinal, neurological, neuromuscular disorders, endocrinological, immunological, psychiatric or cardiovascular disease, myopathies, and bleeding tendency.
- •Problems with hearing and/or balance.
- •Previous injury or surgery to the middle or inner ears, family history of hearing loss before the age of
- •Genetic predisposition to aminoglycoside-driven ototoxicity.
- •Laboratory values outside the reference range that are of clinical relevance.
- •Positive test for HIV antibodies, hepatitis B-virus surface antigen, or anti-hepatitis C-virus antibodies.
- •Blood or plasma donation of 500 mL within 3 months or more than 100 mL within 30 days before signing an informed consent to this trial.
- •Judged by the investigator to have occupational noise exposure of high risk during the trial.
- •Positive test for SARS-CoV-2.
研究组 & 干预措施
Placebo
Physiological saline, solution for infusion.
干预措施: Placebo injection (Drug)
Apramycin injection in escalating doses
Apramycin, solution for infusion.
干预措施: Apramycin injection (Drug)
结局指标
主要结局
Type and incidence of TEAEs related to auditory and vestibular function tests.
时间窗: until 3 months after dosing
Number of subjects with clinically significant observation in physical examination.
时间窗: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Type and incidence of treatment-emergent adverse events (TEAEs) until 2 weeks after dosing.
时间窗: until 2 weeks after dosing
Number of subjects with clinically significant vital sign measurement pulse rate.
时间窗: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Number of subjects with clinically significant vital sign measurement blood pressure.
时间窗: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Number of subjects with clinically significant changes in clinical laboratory parameters.
时间窗: until 2 weeks after dosing
Frequency is defined as number of subjects with clinically significant observations.
Number of subjects with clinically significant changes in ECG parameters.
时间窗: until 2 weeks after dosing
ECG parameters include heart rate and PQ, QT, RS. Frequency is defined as number of subjects with clinically significant observations.
次要结局
未报告次要终点