E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of peripheral tinnitus following traumatic cochlear injury or otitis media |
Léčba periferního tinitu po traumatickém poranění vnitřního ucha nebo zánětu středního ucha |
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E.1.1.1 | Medical condition in easily understood language |
ringing in the ears |
zvonění v uších |
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E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043882 |
E.1.2 | Term | Tinnitus |
E.1.2 | System Organ Class | 10013993 - Ear and labyrinth disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
Primárním cílem studie je vyhodnocení bezpečnosti a lokální snášenlivosti až 3 čtvrtletních léčebných cyklů, přičemž každý z nich sestává ze 3 opakovaných dávek přípravku AM 101 0,87 mg/ml u subjektů dříve léčených v rámci studie TACTT2, a to buď přípravkem AM-101 0,87 mg/ml, nebo placebem. |
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E.2.2 | Secondary objectives of the trial |
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. |
Sekundárním cílem studie je vyhodnocení účinnosti až 3 léčebných cyklů, přičemž každý z nich sestává ze 3 opakovaných dávek přípravku AM 101 0,87 mg/ml u subjektů dříve léčených buď přípravkem AM-101 0,87 mg/ml, nebo placebem. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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).
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Occurrence of deterioration of hearing threshold ≥ 15 dB from baseline (TV1) to TV2, TV3, FUV1 and FUV3 at the average of two contiguous test frequencies in the treated ear. In addition from TV4 to TV5, TV6, FUV4 and FUV6 for all subjects who perform Treatment Cycle 2 and from TV7 to TV8, TV9, FUV7 and FUV9 for all subjects who perform Treatment Cycle 3. It will be evaluated with air and bone conduction hearing threshold values;
• Occurrence of deterioration in hearing threshold ≥ 15 dB at the average of two contiguous test frequencies from baseline (TV1) to FUV5 for all subjects who perform Treatment Cycles 1 and 2 and from baseline (TV1) to FUV8 for all subjects who perform Treatment Cycles 1, 2 and 3. It will be evaluated with air and bone conduction hearing threshold values;
• Difference in occurrence of deterioration of hearing threshold ≥ 15 dB from baseline (TV1) to TV2, TV3, FUV1, FUV2 and FUV3 at the average of two contiguous test frequencies between treated and untreated contralateral ear (subjects with unilaterally treated tinnitus only). In addition from TV4 to TV5, TV6, FUV4, FUV5 and FUV6 for all subjects who perform Treatment Cycle 2 and from TV7 to TV8, TV9, FUV7, FUV8 and FUV9 for all subjects who perform Treatment Cycle 3. It will be evaluated with air and bone conduction hearing threshold values;
• Difference in occurrence of deterioration in hearing threshold ≥ 15 dB from baseline (TV1) to FUV5 at the average of two contiguous test frequencies between treated and untreated contralateral ear (subjects with unilaterally treated tinnitus only) for all subjects who perform Treatment Cycles 1 and 2 and from baseline (TV1) to FUV8 for all subjects who perform Treatment Cycles 1, 2 and 3. It will be evaluated with air and bone conduction hearing threshold values;
• Occurrence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), differentiated by relatedness, and by treatment-emergence and procedure-emergence.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
open-label extension study to TACTT2 (Eudra-CT no. 2013-005587-26) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Czech Republic |
Korea, Democratic People's Republic of |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |