First-In-Human Study of Apramycin

NCT04105205 | Completed Phase 1 DMC

• 1 other identifier: JUV18-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Anti-Bacterial Agents

Outcome Measures

Primary Outcomes (7)

• 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.

  Frequency is defined as number of subjects with clinically significant observations.

  until 2 weeks after dosing

• Number of subjects with clinically significant vital sign measurement pulse rate.

  Frequency is defined as number of subjects with clinically significant observations.

  until 2 weeks after dosing

• Number of subjects with clinically significant observation in physical examination.

  Frequency is defined as number of subjects with clinically significant observations.

  until 2 weeks after dosing

• Number of subjects with clinically significant changes in clinical laboratory parameters.

  Frequency is defined as number of subjects with clinically significant observations.

  until 2 weeks after dosing

• Number of subjects with clinically significant changes in ECG parameters.

  ECG parameters include heart rate and PQ, QT, RS. Frequency is defined as number of subjects with clinically significant observations.

  until 2 weeks after dosing

Study Arms (2)

Apramycin injection in escalating doses

EXPERIMENTAL

Apramycin, solution for infusion.

Drug: Apramycin injection

Placebo

PLACEBO COMPARATOR

Physiological saline, solution for infusion.

Drug: Placebo injection

Interventions

Apramycin injection DRUG

30-min infusion

Apramycin injection in escalating doses

Placebo injection DRUG

30-min infusion

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Juvabis AG: lead
• Innovative Medicines Initiative: collaborator

Study Sites (1)

CRS Clinical Research Services Mannheim GmbH

Mannheim, Germany

Location

Related Publications (1)

• Roch M, Sierra R, Sands K, Martins WMBS, Schrenzel J, Walsh TR, Gales AC, Andrey DO. Vertical and horizontal dissemination of an IncC plasmid harbouring rmtB 16S rRNA methylase gene, conferring resistance to plazomicin, among invasive ST258 and ST16 KPC-producing Klebsiella pneumoniae. J Glob Antimicrob Resist. 2021 Mar;24:183-189. doi: 10.1016/j.jgar.2020.12.006. Epub 2020 Dec 26.

  PMID: 33373732 DERIVED

MeSH Terms

Interventions

apramycin

Study Officials

• Armin Schultz, Dr.med.

  CRS Clinical Research Services Mannheim GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: September 26, 2019
• Study Start: September 25, 2019
• Primary Completion: July 16, 2020
• Study Completion: October 16, 2020
• Last Updated: February 23, 2021

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)