Acute inner ear tinnitus following acute acoustic trauma, sudden deafness, or acute otitis media. MedDRA version: 13.1 Level: PT Classification code 10043882 Term: Tinnitus System Organ Class: 10013993 - Ear and labyrinth disorders
Conditions
Interventions
Product Name: AM-101
Pharmaceutical Form: Gel for injection
INN or Proposed INN: Esketamine hydrochloride
CAS Number: 33643-47-9
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: e
Sponsors
Auris Medical AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Persistent tinnitus following acute acoustic trauma, sudden deafness, or acute otitis media with onset less than three months ago (i.e. acute tinnitus) • Tinnitus provoking incident of acute acoustic trauma, sudden deafness, or acute otitis media is documented by medical report • Minimum Masking Level (MML) of at least 5 dB SL • Age = 18 years and = 65 years • Negative pregnancy test for women of childbearing potential • Willing and able to attend the on-study visits • Must be able to read and understand the relevant study documents • Written informed consent before participation in the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Tinnitus that is not completely maskable • Fluctuating tinnitus • Intermittent tinnitus • Meniere’s Disease • Acute or chronic otitis media or otitis externa • Any ongoing therapy known as potentially tinnitus-inducing (e.g. aminoglycosides, cisplatin, loop diuretics, high doses of aspirin, quinine etc.) • Any drug-based therapy for inner ear hearing loss that is ongoing or was performed in the past 2 weeks, e.g. prednisolone, dexamethasone, pentoxyfilline, betahistine, diazepam, carbamazepine, sodium valproate and antidepressants • Any drug-based therapy for otitis media that is ongoing or was performed in the past 2 weeks • Concomitant use of any other NMDA receptor antagonist (e.g. memantine, dextromethorphan, ifenprodil) • Any ongoing or planned concomitant medication for the treatment of tinnitus until 90 days after study drug application • History or presence of drug abuse or alcoholism • Any clinically relevant respiratory, cardiovascular, neurological (except vertigo), or psychiatric disorder • Known hypersensitivity, allergy or intolerance to the study medication or any history of severe abnormal drug reaction • Women who are breast-feeding, pregnant or who plan a pregnancy during the trial • Women of childbearing potential who declare being unwilling or unable to practice contraception such as hormonal contraceptives, sexual abstinence or intercourse with a vasectomised partner • Concurrent participation in another clinical trial with an investigational drug or participation in another clinical trial with an investigational drug within 30 days prior to study entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is the evaluation of the therapeutic benefit of three repeated dose intratympanic AM-101 injections in comparison to placebo in the treatment of persistent acute inner ear tinnitus following acute acoustic trauma, sudden deafness or acute otitis media.;Secondary Objective: The secondary objectives of the study are (a) safety and local tolerance of intratympanically applied AM-101 injections and (b) identification of the optimal dose of AM-101 in the treatment of persistent acute inner ear tinnitus from acute acoustic trauma, sudden deafness or acute otitis media.;Primary end point(s): The primary efficacy endpoint is defined as follows: Y : delta MML(SL) = MML(SL) (Day0) - MML(SL) (Day90), i.e. the absolute improvement of the sensation level (dB SL) of the minimum masking level (MML) between D0 and D90. Co-primary endpoints are defined as follows: The therapeutic effect will be assessed by two questions to the patients concerning their tinnitus perception: W : delta TLQ = Score TLQ (Day0) - Score TLQ (Day90), i.e. the improvement of the score of the tinnitus loudness question (TLQ) given on a scale from 0 to 100 by the patients between Day 0 and D 90. Z : delta TLQ = Score TAQ (Day0) - Score TAQ (Day90), i.e. the improvement of the score of the tinnitus annoyance question (TAQ) given on a scale from 0 to 100 by the patients between Day 0 and Day 90. Primary safety endpoints: Change in hearing threshold = 15 dB from baseline to Day7, Day30, and Day90 in any two contiguous test frequencies in the treated ear. Primary safety endpoint is the Day 30 visit. ;Timepoint(s) of evaluation of this end point: Day 0, Day 7, Day 30, and Day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: The following secondary endpoints are defined that focus on other aspects of tinnitus impair-ment as well as on tinnitus disability and handicap: • V : delta LM(SL) = LM(SL) (Day0) - LM(SL) (Day90), i.e. the absolute improvement of the sensation level (dB SL) of the tinnitus loudness match (LM) between Day0 and Day90. • Complete recovery rate, i.e. the percentage of patients who recover on Day90 to a MML(SL) of 0 dB (no tinnitus anymore). • Partial recovery rate, i.e. the percentage of patients who show at least 50% improvement in the MML(SL) between Day0 and Day90: [MML(SL)(Day0) – MML(SL)(Day90)] / MML(SL)(Day0) x 100 = 50%. • Global impression of change questionnaire for tinnitus severity at study completion (Day90). • The change in tinnitus handicap from baseline as measured by the TBF-12 questionnaire at Day90. • The change in sleep impact by magnitude estimation from baseline to Day90 as assessed by three questions concerning sleeping difficulties, each assessed on a scale from 0 to 100 Secondary safety endpoint: Percent and distribution of severity of Adverse Events (AE) and Serious Adverse Events (SAE);Timepoint(s) of evaluation of this end point: Day0, Day7, Day 30, and Day 90. | — |
Countries
Belgium, Germany, Netherlands
Outcome results
None listed