Study to observe long-term safety of AM-101 in patients with tinnitus

Phase 1

Conditions: Treatment of peripheral tinnitus following traumatic cochlear injury or otitis media
MedDRA version: 19.0Level: PTClassification code 10043882Term: TinnitusSystem Organ Class: 10013993 - Ear and labyrinth disorders
Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]

Registration Number: EUCTR2013-005588-24-CZ

Lead Sponsor: Auris Medical Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 330

Inclusion Criteria

A subject will be eligible for this study if all of the following criteria apply:
1. Attendance of the final visit FUV3 of study AM 101-CL-12-01 (TACTT2);
TV1 of AMPACT1 should preferably be conducted within 48 hours of FUV3 of TACTT2, but no later than 14 days thereafter.
2. Negative urine pregnancy test for women of childbearing potential;
3. Willing and able to attend the study visits during at least one treatment cycle;
4. Able to read and understand study documents, to complete the relevant questionnaires and rating scales and follow Investigator instructions;
5. Able to understand and follow study personnel instructions during audiologic measurements;
6. 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;
7. 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;
8. 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 this study if any of the following criteria apply:
1. Study drug related or procedure related adverse event leading to treatment discontinuation in study AM 101-CL-12-01 (TACTT2);
2. Suspected or diagnosed Meniere’s Disease, endolymphatic hydrops, acoustic neuroma or history of fluctuating hearing loss;
3. Ongoing purulent acute or chronic otitis media or otitis externa;
4. Abnormality of the tympanic membrane in the affected ear(s) that would preclude i.t. injection;
5. 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);
6. Any ongoing drug-based therapy for otitis media or otitis externa;
7. 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 enrollment into the open-label study (TV1, D0), or that is ongoing or planned for the study duration;
8. Use of any other NMDA receptor antagonist (e.g. memantine, dextromethorphan) that is planned for the study duration;
9. Any planned pharmacological or non-pharmacological treatment of tinnitus for the study duration;
10. History within the past two years or presence of drug abuse or alcoholism;
11. 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 TACTT2 study prior to enrollment into the open-label study (TV1, D0) for these diseases;
12. Use of any antidepressant or anti-anxiety medication in the past 2 weeks prior to enrollment into the open-label study (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 during the previous TACTT2 study prior to enrollment into the open-label study (TV1, D0), not for the treatment of tinnitus, and if the treatment will be maintained throughout the duration of the study;
13. Any clinically relevant respiratory, cardiovascular, neurological disorder (except vertigo), as determined by the Investigator;
14. Any clinically relevant abnormalities in physical examination on Day 0 (TV1, D0);
15. Women who are breast-feeding, pregnant or who are planning to become pregnant during the study;
16. 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;
17. Involvement or planned involvement in legal action related to the present peripheral tinnitus during the course of the study;
18. Concurrent participation in another clinical study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is the evaluation of the safety and local tolerance of up to 3 quarterly treatment cycles each with 3 repeated doses of AM-101 0.87 mg/mL in subjects previously treated in the scope of the TACTT2 study with either AM-101 0.87 mg/mL or placebo.;Secondary Objective: The secondary objective of the study is the assessment of the efficacy of up to 3 treatment cycles each with 3 repeated doses of AM-101 0.87 mg/mL in subjects previously treated with either AM-101 0.87 mg/mL or placebo.;Primary end point(s): • Occurrence of deterioration in hearing threshold = 15 dB from before the start of each treatment cycle (TV1, TV4, TV7) to the corresponding 35-day-Follow-Up Visit of the respective treatment cycle (FUV2, FUV5 or FUV8) at the average of two contiguous test frequencies in the treated ear. It will be evaluated with air and bone conduction hearing threshold values.;Timepoint(s) of evaluation of this end point: last follow-up visit

Secondary Outcome Measures