AM-101 in the Treatment of Acute Tinnitus 2

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.

Detailed Description
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This phase III study is assessing the drug's safety and is aiming to demonstrate efficacy of repeated intratymanic AM-101 injections in the treatment of acute peripheral tinnitus (up to 3 months from onset).

Official Title
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Efficacy and Safety of AM-101 in the Treatment of Acute Peripheral Tinnitus 2

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 prior to randomization Age ≥ 18 years and ≤ 75 years (≥ 14 years and ≤ 75 years at selected sites); 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: Change in Patient-reported Tinnitus Loudness Questionnaire (TLQ) Improvement From Baseline to Follow up Visit 3 (FUV3) | Starting at the screening visit (SV), each subject recorded the following numerical rating scales (NRS) throughout the entire study duration: - Tinnitus loudness at its loudest within the last 24 hours (Tinnitus Loudness Questionnaire [TLQ] NRSLoudest). Subjects were asked On a scale from 0 to 10, where 0 represents no tinnitus and 10 represents extremely loud tinnitus, what one number best describes your tinnitus at its loudest in the last 24 hours (including right now)? TLQ NRSLoudest was collected from SV (D-14) to the evening before FUV3 (D83). The ratings were to be recorded every day before going to sleep on an electronic device. As Baseline the10 ratings of the screening period before the first treatment were averaged. For the FUV3 endpoint, the ratings of the 7 days before FUV3 were averaged. | Screening (D-14) versus final follow-up (D83) | 
| Co-Primary Efficacy: Improvement in Tinnitus Functional Index (TFI) Total Score From Baseline to FUV3 | The TFI was recorded on an electronic device (electronic patient reported outcome) at Treatment Visit 1 (TV1), before randomization, and at Follow up Visit 1 (FUV1), FUV2 and FUV3. The TFI is a patient reported outcome questionnaire and contains 25 questions. It includes eight subscales: Intrusive, Sense of Control, Cognitive, Sleep, Auditory, Relaxation, Quality of Life, and Emotional. Each question is to be rated on a NRS between 0 and 10 (or 0 to 100%), with a recall period of over the past week. The TFI total score is considered as valid if there are evaluable answers for at least 19 of the 25 items (76% of items) (Meikle et al. 2012). The repondent's overall TFI score is within a 0-100 range. For the subscales the range is the same. A lower value represents an improvement for all scales. Please refer to the following publicly available link for more information: http://download.lww.com/wolterskluwer_vitalstream_com/PermaLink/EANDH/A/EANDH_2011_09_27_HENRY_200593_SDC15.pdf | D0 (=TV1) versus Day 84 (=FUV3) | 
| Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2) | Occurence of deterioration of hearing (Air and Bone conduction) in the treated ear at FUV2. Deterioration is defined as a deterioration of hearing threshold of at least 15 dB from Baseline at the average of 2 contiguous frequencies. | Day 35 |