AM-101 in the Treatment of Acute Tinnitus 3

Study Overview
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Brief Summary
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The purpose of this research study is to test the safety and effectiveness of the study drug, AM-101. AM-101 is tested for the treatment of tinnitus that started as the result of an injury to the inner ear or due to middle ear inflammation (otitis media). Subjects with tinnitus can take part in the study, if their tinnitus started within the last 3 months or within the last >3 to 6 months.

Detailed Description
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This phase III study is assessing the drug's safety and is aiming to demonstrate efficacy of repeated intratympanic AM-101 injections in the treatment of acute peripheral tinnitus (up to 3 months (Stratum A), or between >3 and 6 months (Stratum B) from onset).

Official Title
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Efficacy and Safety of AM-101 in the Treatment of Acute Peripheral Tinnitus 3

Conditions
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Tinnitus

Intervention / Treatment
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* Drug: AM-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent subjective peripheral tinnitus (unilateral or bilateral) following traumatic cochlear injury (acute acoustic trauma, blast trauma, middle ear surgery, inner ear barotrauma, tympanic membrane trauma) or otitis media with onset no longer than 3 months (Stratum A) or between >3 months and 6 months (Stratum B) prior to randomization, as documented by medical report or by documented medical history. Upon implementation of protocol amendment 6, subjects with tinnitus following traumatic cochlear injury will only be eligible if they are affected only unilaterally. Age ≥ 18 years and ≤ 75 years; Negative pregnancy test (woman of childbearing potential); Willing and able to use adequate hearing protection, respectively to refrain from engaging in activities or work involving loud noise exposure where sufficient hearing protection is not possible or ensured; Willing and able to protect ear canal and middle ear from water exposure as long as tympanic membrane is not fully closed. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Fluctuating tinnitus; Intermittent tinnitus; Tinnitus resulting from traumatic head or neck injury; Presence of chronic tinnitus; Meniere's Disease, history of endolymphatic hydrops, or history of fluctuating hearing loss; History of repeated idiopathic sudden sensorineural hearing loss or history of acoustic neuroma; Ongoing acute or chronic otitis media or otitis externa; Other treatment of tinnitus for the study duration; 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 are planning to become pregnant during the study; Women of childbearing potential who are unwilling or unable to practice contraception, such as hormonal contraceptives, double barrier, sexual abstinence or intercourse with a partner who has been vasectomised for at least three months; Concurrent participation in another clinical study or participation in another clinical study within 30 days prior to randomization. Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AM-101 injection<br>AM-101 | Drug: AM-101<br>* AM-101 gel for intratympanic injection<br>|
| Placebo Comparator: Placebo injection<br>Placebo | Drug: Placebo<br>* Placebo gel for intratympanic injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoint - alternate primary efficacy endpoints: Tinnitus Functional Index (TFI) | Improvement in TFI total score | Baseline to Day 84 | 
| Efficacy endpoint - alternate primary efficacy endpoints: Patient-reported Tinnitus loudness on a Numerical Rating Scale (TLQ NRS loudest) | Improvement in TLQ NRS loudest | Baseline to Day 84 | 
| Safety endpoint: Hearing threshold | Occurrence of deterioration in hearing threshold >= 15 decibel (dB) at the average of two contiguous test frequencies (air conduction) in the treated ear(s) | Baseline to Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoint - TFI | Improvement in TFI total score | Baseline to Day 10 and Day 35 | 
| Efficacy endpoint - TLQ NRS loudest | Improvement in patient-reported tinnitus loudness | Baseline to Day 10 and Day 35 | 
| Efficacy endpoint - patient-reported tinnitus annoyance (TAQ NRS worst) | Improvement in TAQ NRS worst | Baseline to Day10, Day 35 and Day 84 | 
| Efficacy endpoint - TFI sleep score | Improvement in TFI sleep score. The subscale sleep will be evaluated only for subjects with a TFI Sleep score greater than 0 at baseline. | Baseline to Day10, Day 35 and Day 84 | 
| Efficacy endpoint - Patient global impression of change in tinnitus severity (PGIC Tinnitus) | Patient global impression of change in tinnitus severity | at Day10, Day 35 and Day 84 | 
| Safety endpoint - Hearing threshold | Occurrence of deterioration in hearing threshold >= 15 dB at the average of two contiguous test frequencies in the treated ear(s) | Baseline to Day 1, Day 2, Day 10 and Day 84 | 
| Safety endpoint - Hearing threshold | Difference in occurrence of deterioration in hearing threshold >= 15 dB at the average of two contiguous test frequencies between the treated and untreated contralateral ear (subjects with unilaterally treated tinnitus only) | Baseline to Day 1, Day 2, Day 10 and Day 84 | 
| Safety endpoint - AEs and SAEs | Occurence and severity of adverse events (AEs) and serious adverse Events (SAEs), differentiated by relatedness, and by treatment-emergence and procedure-emergence | Up to Day 84 |