Healthy Volunteers
Conditions
Keywords
Anti-Bacterial Agents
Brief summary
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.
Interventions
DRUGApramycin injection
30-min infusion
DRUGPlacebo injection
30-min infusion
Sponsors
Innovative Medicines Initiative
Juvabis AG
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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 m2. * 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.
Exclusion criteria
* 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 60. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type and incidence of treatment-emergent adverse events (TEAEs) until 2 weeks after dosing. | until 2 weeks after dosing | — |
| Type and incidence of TEAEs related to auditory and vestibular function tests. | until 3 months after dosing | — |
| Number of subjects with clinically significant vital sign measurement blood pressure. | 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 pulse rate. | until 2 weeks after dosing | Frequency is defined as number of subjects with clinically significant observations. |
| Number of subjects with clinically significant observation in physical examination. | 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. | 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. | 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. |
Countries
Germany
Outcome results
None listed