Study to observe efficacy and safety of AM-101 in patients with tinnitus

Phase 1

• Conditions: MedDRA version: 18.0Level: PTClassification code 10043882Term: TinnitusSystem Organ Class: 10013993 - Ear and labyrinth disorders; Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]; Acute peripheral tinnitus following traumatic cochlear injury or otitis media

• Registration Number: EUCTR2013-005587-26-CZ
• Lead Sponsor: Auris Medical Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-05
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 330

Inclusion Criteria

A subject will be eligible for inclusion in this study if all of the
following criteria apply:
1. 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, as documented by medical report or by documented medical history.
Persistent tinnitus is given when the question, When you were thinking of your tinnitus in the past two weeks, could you always hear it or only sometimes?” is answered with Always”, and the question, Did your tinnitus in the past two weeks occur all of the
time, most of the time, a good bit of the time, some of the time, a little of the time, none of the time?” is answered with All of the time” or Most of the time” or A good bit of the time”. The words, past two weeks may be replaced with since onset” if tinnitus
started less than two weeks ago.
2. Age = 18 years and = 75 years;
3. Negative urine pregnancy test for women of childbearing potential;
4. Willing and able to attend the study visits;
5. Able to read and understand study documents, to complete the relevant questionnaires and rating scales and follow Investigator instructions;
6. Able to understand and follow study personnel instructions during audiologic measurements;
7. 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;
8. Willing and able to protect ear canal and middle ear from water exposure as long as tympanic membrane is not fully closed after IMP administration;
9. Signed IRB/REB/IEC approved Informed Consent Form (ICF).
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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the
following criteria apply:
1. Fluctuating tinnitus;
Fluctuating tinnitus is given when the question Over the last 2 weeks, has the pitch of your tinnitus [risen / decreased / fluctuated / remained steady / not clear]?” is answered with fluctuated” or not clear”.
2. Intermittent tinnitus;
Intermittent tinnitus is given when the question When you were thinking of your tinnitus in the past two weeks, could you always hear it or only sometimes?” is answered with only sometimes”.
3. Tinnitus resulting from traumatic head or neck injury;
4. Onset of tinnitus more than 3 months ago;
5. Suspected or diagnosed Meniere’s Disease, history of endolymphatic hydrops, or history of fluctuating hearing loss;
6. History of repeated idiopathic sudden sensorineural hearing loss (defined as at least two events of ISSNHL in the last 24 months) or history of acoustic neuroma;
7. Ongoing purulent acute or chronic otitis media or otitis externa;
8. Abnormality of the tympanic membrane in the affected ear(s) that would preclude i.t. injection;
9. Subjects with current hearing loss in the affected ear(s) of 75 dB or more in one or more test frequencies (250 Hz, 500 Hz, 1 kHz, 2 kHz, 3 kHz, 4 kHz, 6 kHz, 8 kHz);
10. Subjects with fluctuating hearing (=20 dB difference in any two contiguous test frequencies over the screening period; SV, D-14 to TV1, D0);
11. Any drug-based therapy for otitis media or otitis externa that is ongoing or was performed in the past two weeks prior to randomization (TV1, D0);
12. Any drug-based therapy known as potentially tinnitus-inducing (e.g. aminoglycosides, cisplatin, loop diuretics, high doses of aspirin [> 2 g/day] or quinine) in the past 2 weeks prior to randomization (TV1, D0) or that is ongoing or planned for the study duration;
13. Use of any other NMDA receptor antagonist (e.g. memantine, dextromethorphan) in the past 2 weeks prior to randomization (TV1, D0), or that is ongoing, or that is planned for the study duration;
14. Any ongoing or planned pharmacological or non-pharmacological treatment of tinnitus for the study duration;
15. History within the past two years or presence of drug abuse or alcoholism;
16. Subjects with diagnosed anxiety disorders, depression, bipolar disorder, schizophrenia or other significant psychiatric diseases requiring current drug treatment or subjects who required treatment in the previous 3 months prior to randomization (TV1, D0) for these
diseases;
17. Use of any antidepressant or anti-anxiety medication in the past 2 weeks prior to randomization (TV1, D0), or that is ongoing, or that is planned for the study duration unless the medication was taken in a low dose and permanently for at least 3 months prior to
randomization (TV1, D0), not for the treatment of tinnitus, and if the treatment will be maintained throughout the duration of the study;
18. Any clinically relevant respiratory, cardiovascular, neurological disorder (except vertigo), as determined by the Investigator;
19. Any clinically relevant abnormalities in laboratory test or physical examination prior to randomization;
20. Known hypersensitivity, allergy or intolerance to the study medication or any history of severe, abnormal drug reaction;
21. Women who are breast-feeding, pregnant or who are planning to become pregnant during the study;
22. Women of childbearing potential who are unwilling or unable to practice contracepti

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: The secondary objective of the study is the further assessment of the safety and local tolerance of repeated i.t. AM-101 injections in the treatment of acute peripheral tinnitus.;Primary end point(s): Primary efficacy endpoints:<br>? Improvement in patient-reported tinnitus loudness TLQ NRSLoudest from baseline to FUV3;<br>? Improvement in TFI total score from baseline to FUV3.;Timepoint(s) of evaluation of this end point: Last follow-up visit (FUV3);Main Objective: The primary objective of the study is the evaluation and confirmation of the efficacy of repeated i.t. AM-101 injections in the treatment of acute peripheral tinnitus

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary efficacy endpoints:<br>? Improvement in patient-reported tinnitus loudness TLQ NRSLoudest from baseline to FUV1 and FUV2;<br>? Improvement in TFI total score from baseline to FUV1 and FUV2.;Timepoint(s) of evaluation of this end point: Last follow-up visit (FUV3)