hearing impairment now healty volunteers) tinnitus (at a later stage
Conditions
Interventions
Single intratympanic injection with study medication
Sponsors
AudioCure Pharma GmbH
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Signed Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved informed consent form (ICF) 2. Willing and able to attend the trial visits 3. Able to read and understand trial documents and follow Investigator and trial personnel instructions during visits, including audiology measurements 4. Female or male 5. Age * 18 years and * 40 years at the day of Screening 6. Body mass index (BMI) 18.0 - 30.0 kg/m2, inclusive, where BMI (kg/m2)
Exclusion criteria
Exclusion criteria: 1. History of acute hearing loss from noise trauma, barotrauma or head trauma in either ear at any time 2. History of idiopathic sudden sensorineural hearing loss in the past 2 years 3. Congenital hearing loss 4. History of chronic (> 6 months) noise exposure (for leisure or profession) 5. Chronic or acute tinnitus in either ear 6. Current vertigo/previous balance or vestibular disorders 7. Any clinically significant external or middle-ear pathology observed by otoscopic examination or tympanometry (i.e. reduced mobility of the tympanic membrane) 8. Any clinically significant abnormality of the tympanic membrane or the outer ear canal in the selected ear that would preclude intratympanic administration 9. Absence of detectable OAEs in the frequency band with a concomitant clinically significant increase in hearing thresholds in accordance with DIN EN ISO 8253-1 and DIN 7029:2017 10. Known family history of hearing impairment, other than age related 11. History of autoimmune hearing loss, radiation-induced hearing loss, fluctuating hearing, endolymphatic hydrops or Menière*s disease in either ear 12. History of chronic inflammatory or suppurative ear disease or cholesteatoma 13. Current evidence or history of acoustic neuroma or other retrocochlear damage 14. History of otosclerosis 15. Suspected perilymph fistula or membrane rupture in either ear 16. Otitis media or otitis externa that is ongoing or ended within 30 days prior to study treatment or is occurring several times per year 17. Radiation therapy in the head and neck area 18. Any therapy known as ototoxic (e.g. aminoglycosides [systemic or ototopical], cisplatin, loop diuretics, quinine etc.) 19. Taking any anti-coagulant medication (direct oral anticoagulant [DOAC], e.g. Apixaban®), vitamin K antagonists (e.g. Marcumar®), thrombocyte aggregation blockers (e.g. Aspirin®) chronically or Aspirin® as a pain killer acutely within one week before treatment 20. History or presence of drug abuse or alcoholism within the past 2 years 21. Positive urine screen of drugs of abuse (if not due to concomitant medication, e.g. benzodiazepines as hypnotics) or alcohol breath test at Screening or Day -1 22. Ingestion of alcohol within 48 hours prior to study medication administration and during the in-house period. 23. Current smokers 24. Excess in xanthine consumption (more than 5 cups of coffee/day or equivalent) 25. Subjects with diagnosed anxiety disorders, psychosis, depression, schizophrenia, attempted suicide or other significant psychiatric conditions that can impact their ability to cooperate and comply with the study protocol 26. Any clinically relevant autoimmune, respiratory, cardiovascular, hepatic, gastrointestinal, renal, dermatological, neurological or other abnormality that in the opinion of the Investigator may pose a safety risk to a subject in this study, which may confound safety assessment, or may interfere with study participation or the evaluation of study treatment 27. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection 28. Having an active infection with SARS-CoV-2 29. Abnormal and clinically relevant laboratory results 30. Systemic steroids within the last three months (topical steroids like nasal spray or cremes are allowed) 31. Seated pulse rate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Endpoints: * Treatment-emergent (serious) adverse events (TE(S)AEs) * Treatment emergent adverse events of special interest (AESIs): o Permanent sensorineural hearing loss o Persistent conductive hearing loss o Persistent tinnitus o Persistent vestibular vertigo o Persistent tympanic membrane perforation o Infections of the outer, middle and inner ear * Concomitant medication * Clinical laboratory tests: o Hematology o Biochemistry o Urinalysis * Vital signs: o Pulse rate (bpm) o Systolic and diastolic blood pressure (mmHg) o Body temperature * ECG: o Heart rate (HR) (beats per minute [bpm]), QTcF Pharmacokinetic endpoints: The following endpoints will be determined for AC102 by non-compartmental analysis of the plasma concentration-time data: * The area under the plasma concentration-time curve from zero to infinity (AUC0-inf) * The maximum plasma concentration (Cmax) * The area under the plasma concentration-time curve from zero to t of the last measured concentration above the limit of quantification (AUC0-last) * The time to reach maximum plasma concentration (tmax) * The terminal disposition rate constant (*z) with the respective half-life (t*) * Other parameters, including apparent volume of distribution (Vz/F), apparent total body clearance (CL/F), and other parameters as appropriate and possible, as well as dose adjusted parameters, may be determined. | — |
Countries
Netherlands
Outcome results
None listed