Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AM-101 injection | Experimental | AM-101 |
|
| Placebo injection | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AM-101 | Drug | AM-101 gel for intratympanic injection |
| |
| 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. |
Not provided
Not provided
Inclusion Criteria:
Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
Other protocol-defined exclusion criteria may apply.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medpace | Cincinnati | Ohio | 45227 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28608739 | Result | Staecker H, Morelock M, Kramer T, Chrbolka P, Ahn JH, Meyer T. Safety of Repeated-Dose Intratympanic Injections with AM-101 in Acute Inner Ear Tinnitus. Otolaryngol Head Neck Surg. 2017 Sep;157(3):478-487. doi: 10.1177/0194599817711378. Epub 2017 Jun 13. |
Not provided
Not provided
A total of 478 subjects were screened, 343 subjects were randomized, and 336 subjects were treated. 7 subjects were randomized (3 to AM-101 and 4 to placebo) but not treated; these subjects were excluded from the analysis sets.
The majority (92%) of subjects completed the study.
A total of 86 sites were initiated in Canada, the United States, the Czech Republic, Israel, Turkey and Republic of South Korea. In total, 69 sites screened each at least 1 subject and 64 sites randomized subjects for treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | AM-101 0.87 mg/mL Gel | Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4) |
| FG001 | Placebo Gel | Three intratympanic administration of placebo gel within 5 days (D0-D4). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | AM-101 0.87 mg/mL Gel | Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4) |
| BG001 | Placebo Gel | Three intratympanic administration of placebo gel within 5 days (D0-D4). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Valid for Efficacy dataset includes all subjects treated with at least one i.t. injection (AM-101 or placebo), a valid TLQ NRSLoudest or TFI rating at baseline and at least one valid post-baseline rating. Ten subjects had neither TLQ nor TFI baseline and 2 subjects had no valid rating for the TLQ resulting in 324 evaluable subjects. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Screening (D-14) versus final follow-up (D83) |
Assessed by Investigator at all Visits from Screening Visit (SV, D-14) to end of treatment visit FUV3 (D84). Including at treatment visit 1 (TV1), TV2, TV3, FUV1 and FUV2. It was also assessed at Conditional Visits if they were required.
Safety population includes 336 instead of 343 subjects. As 7 subjects were randomized but not treated (see pre-assignment details).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AM-101 0.87 mg/mL Gel | Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Meyer, CEO | Auris Medical Inc. | +1 312 396 4150 | hear@aurismedical.com |
Not provided
| ID | Term |
|---|---|
| D014012 | Tinnitus |
| ID | Term |
|---|---|
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000592906 | PDCD5 protein, rat |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo |
| Drug |
Placebo gel for intratympanic injection |
|
| Day 35 |
| Withdrawal by Subject |
|
| Randomization error |
|
| Lost to Follow-up |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
|
| Primary | 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 | Valid for Efficacy dataset includes all subjects treated with at least one i.t. injection (AM-101 or placebo), a valid TLQ NRSLoudest or TFI rating at baseline and at least one valid post-baseline rating. Ten subjects had neither TLQ nor TFI baseline plus additional 25 subjects had no baseline for the TFI resulting in 301 evaluable subjects. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | D0 (=TV1) versus Day 84 (=FUV3) |
|
|
|
|
| Primary | 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. | Valid for Safety dataset was used. Of the 336 valid for safety subjects, 323 could be evaluated for this endpoint. | Posted | Count of Participants | Participants | Day 35 |
|
|
|
|
| 0 |
| 201 |
| 5 |
| 201 |
| 63 |
| 201 |
| EG001 | Placebo Gel | Three intratympanic administration of placebo gel within 5 days (D0-D4). | 0 | 135 | 1 | 135 | 38 | 135 |
| Tendon rupture | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| Mental disorder | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tympanic membrane perforation | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
The Investigator agrees to submit a copy of any intended communication, presentation or publication (abstract, poster, article, etc.) (all together "Communication") at least 2 month in advance of the submission of proposed Communication. The Sponsor shall have 60 days, after receipt of said copies, to object to such proposed Communication. In case of such objection, the Investigator shall refrain from making such Communication for 6 months from date of receipt of such objection.
| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Bone conduction |
|
| 1.0 |
| Superiority |