E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute inner ear tinnitus following acute acoustic trauma, sudden deafness, or acute otitis media. |
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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 | 13.1 |
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 | Yes |
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 therapeutic benefit of three repeated dose intratympanic AM-101 injections in comparison to placebo in the treatment of persistent acute inner ear tinnitus following acute acoustic trauma, sudden deafness or acute otitis media. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are (a) safety and local tolerance of intratympanically applied AM-101 injections and (b) identification of the optimal dose of AM-101 in the treatment of persistent acute inner ear tinnitus from acute acoustic trauma, sudden deafness or acute otitis media. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Persistent tinnitus following acute acoustic trauma, sudden deafness, or acute otitis media with onset less than three months ago (i.e. acute tinnitus)
• Tinnitus provoking incident of acute acoustic trauma, sudden deafness, or acute otitis media is documented by medical report
• Minimum Masking Level (MML) of at least 5 dB SL
• Age ≥ 18 years and ≤ 65 years
• Negative pregnancy test for women of childbearing potential
• Willing and able to attend the on-study visits
• Must be able to read and understand the relevant study documents
• Written informed consent before participation in the study
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E.4 | Principal exclusion criteria |
• Tinnitus that is not completely maskable
• Fluctuating tinnitus
• Intermittent tinnitus
• Meniere’s Disease
• Acute or chronic otitis media or otitis externa
• Any ongoing therapy known as potentially tinnitus-inducing (e.g. aminoglycosides, cisplatin, loop diuretics, high doses of aspirin, quinine etc.)
• Any drug-based therapy for inner ear hearing loss that is ongoing or was performed in the past 2 weeks, e.g. prednisolone, dexamethasone, pentoxyfilline, betahistine, diazepam, carbamazepine, sodium valproate and antidepressants
• Any drug-based therapy for otitis media that is ongoing or was performed in the past 2 weeks
• Concomitant use of any other NMDA receptor antagonist (e.g. memantine, dextromethorphan, ifenprodil)
• Any ongoing or planned concomitant medication for the treatment of tinnitus until 90 days after study drug application
• History or presence of drug abuse or alcoholism
• Any clinically relevant respiratory, cardiovascular, neurological (except vertigo), or psychiatric disorder
• 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 plan a pregnancy during the trial
• Women of childbearing potential who declare being unwilling or unable to practice contraception such as hormonal contraceptives, sexual abstinence or intercourse with a vasectomised partner
• Concurrent participation in another clinical trial with an investigational drug or participation in another clinical trial with an investigational drug within 30 days prior to study entry
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as follows:
Y : delta MML(SL) = MML(SL) (Day0) - MML(SL) (Day90),
i.e. the absolute improvement of the sensation level (dB SL) of the minimum masking level (MML) between D0 and D90.
Co-primary endpoints are defined as follows:
The therapeutic effect will be assessed by two questions to the patients concerning their tinnitus perception:
W : delta TLQ = Score TLQ (Day0) - Score TLQ (Day90),
i.e. the improvement of the score of the tinnitus loudness question (TLQ) given on a scale from 0 to 100 by the patients between Day 0 and D 90.
Z : delta TLQ = Score TAQ (Day0) - Score TAQ (Day90),
i.e. the improvement of the score of the tinnitus annoyance question (TAQ) given on a scale from 0 to 100 by the patients between Day 0 and Day 90.
Primary safety endpoints:
Change in hearing threshold ≥ 15 dB from baseline to Day7, Day30, and Day90 in any two contiguous test frequencies in the treated ear. Primary safety endpoint is the Day 30 visit.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 0, Day 7, Day 30, and Day 90 |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints:
The following secondary endpoints are defined that focus on other aspects of tinnitus impair-ment as well as on tinnitus disability and handicap:
• V : delta LM(SL) = LM(SL) (Day0) - LM(SL) (Day90),
i.e. the absolute improvement of the sensation level (dB SL) of the tinnitus loudness match (LM) between Day0 and Day90.
• Complete recovery rate, i.e. the percentage of patients who recover on Day90 to a MML(SL) of 0 dB (no tinnitus anymore).
• Partial recovery rate, i.e. the percentage of patients who show at least 50% improvement in the MML(SL) between Day0 and Day90:
[MML(SL)(Day0) – MML(SL)(Day90)] / MML(SL)(Day0) x 100 ≥ 50%.
• Global impression of change questionnaire for tinnitus severity at study completion (Day90).
• The change in tinnitus handicap from baseline as measured by the TBF-12 questionnaire at Day90.
• The change in sleep impact by magnitude estimation from baseline to Day90 as assessed by three questions concerning sleeping difficulties, each assessed on a scale from 0 to 100
Secondary safety endpoint:
Percent and distribution of severity of Adverse Events (AE) and Serious Adverse Events (SAE) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day0, Day7, Day 30, and Day 90.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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Randomisation and patient enrolment will be stopped, if based on a review of safety and tolerability data by the Safety Officer and after joint consultation between the Safety Officer and the Co-ordinating Investigators, further treatments are deemed not acceptable. |
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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 | 3 |
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 | 3 |