Status:
COMPLETED
First-In-Human Study of Apramycin
Lead Sponsor:
Juvabis AG
Collaborating Sponsors:
Innovative Medicines Initiative
Conditions:
Healthy Volunteers
Eligibility:
All Genders
18-45 years
Phase:
PHASE1
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...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
September 25 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 16 2020
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT04105205
Start Date
September 25 2019
End Date
October 16 2020
Last Update
February 23 2021
Active Locations (1)
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1
CRS Clinical Research Services Mannheim GmbH
Mannheim, Germany