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The purpose of this research study is to test the safety and local tolerance of repeated treatment cycles of AM-101.
This open-label extension study is assessing the safety and local tolerance of repeated treatment cycles of AM-101 in subjects previously treated in the scope of the TACTT2 study (NCT01803646).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AM-101 injection | Experimental | AM-101 gel for intratympanic injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AM-101 | Drug | AM-101 gel for intratympanic injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Subjects With a Deterioration of Hearing Threshold at Day 35 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | Day 1 (TV1) to Day 35 (FUV2) of cycle 1 |
| Frequency of Subjects With a Deterioration of Hearing Threshold at Day 119 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | Day 84 (TV4) to Day 119 (FUV5) of cycle 2 |
| Frequency of Subjects With a Deterioration of Hearing Threshold at Day 203 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | Day 168 (TV7) up to Day 203 (FUV8) of cycle 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Subjects With a Deterioration of Hearing Threshold at Day 84 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. |
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Inclusion Criteria:
Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
Other protocol-defined exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medpace | Cincinnati | Ohio | 45227 | United States |
Main Inclusion Criteria:
A total of 260 subjects were enrolled and 257 subjects were treated in overall 59 active sites in Canada (6), the United States (35), the Czech Republic (7), Israel (2), Turkey (3) and Republic of South Korea (6). Subjects could only participate if they had been previously enrolled and completed the participation in the TACTT2 study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 Cycle AM-101 | Subjects participated in 1 treatment cycle and received one round of 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0-D4) |
| FG001 | 2 Cycles AM-101 | Subjects that participated in 2 treatment cycles of the AMPACT1 study, received 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0 - D4) in cycle 1 and after final follow-up (D84) of cycle 1, they rolled-over to treatment cycle 2 receiving once more 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D84 - D88). |
| FG002 | 3 Cycles AM-101 | Subjects that participated in all 3 treatment cycles of the AMPACT1 study, received 3 x 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days. The subjects could only roll-over if they completed the final follow-up of the previous cycle and were still eligible. In cycle 1 treatment was within D0 - D4. Cycle 2 treatment within D84 - D88. And treatment for cycle 3 within D168-D172. Final follow-up after 3 treatment cycles was FUV9 (D252). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1 Cycle AM-101 | Subjects participated in 1 treatment cycle and received one round of 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0-D4) |
| BG001 | 2 Cycles AM-101 |
| 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 | Frequency of Subjects With a Deterioration of Hearing Threshold at Day 35 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available. | Posted | Number | Number subject affected | Day 1 (TV1) to Day 35 (FUV2) of cycle 1 |
|
From baseline to end of study at all visits, up to Day 252.
Assessed by Investigator at all visits. In non-serious adverse events section, under occurrences (all), reported numbers are "subjects affected".
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1 Cycle AM-101 | Subjects participated in 1 treatment cycle and received one round of 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0-D4) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Liver function test increased | Investigations | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Meyer, CEO | Auris Medical Inc. | +1 312 396 4150 | hear@aurismedical.com |
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| ID | Term |
|---|---|
| D014012 | Tinnitus |
| ID | Term |
|---|---|
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
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| ID | Term |
|---|---|
| C000592906 | PDCD5 protein, rat |
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| Day 1 (TV1) to Day 84 (FUV3) of cycle 1 |
| Frequency of Subjects With a Deterioration of Hearing Threshold at Day 168 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | Day 84 (TV4) to Day 168 (FUV6) of cycle 2 |
| Frequency of Subjects With a Deterioration of Hearing Threshold at Day 252 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | Day 168 (TV7) to Day 252 (FUV9) of cycle 3 |
| Lost to Follow-up |
|
Subjects that participated in 2 treatment cycles of the AMPACT1 study, received 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0 - D4) in cycle 1 and after final follow-up (D84) of cycle 1, they rolled-over to treatment cycle 2 receiving once more 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D84 - D88).
| BG002 | 3 Cycles AM-101 | Subjects that participated in all 3 treatment cycles of the AMPACT1 study, received 3 x 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days. The subjects could only roll-over if they completed the final follow-up of the previous cycle and were still eligible. In cycle 1 treatment was within D0 - D4. Cycle 2 treatment within D84 - D88. And treatment for cycle 3 within D168-D172. Final follow-up after 3 treatment cycles was FUV9 (D252). |
| BG003 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 2 Cycles AM-101 | Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2. |
| OG002 | 3 Cycles AM-101 | Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2. |
|
|
|
| Primary | Frequency of Subjects With a Deterioration of Hearing Threshold at Day 119 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available. Subjects from Cycle 1 did not participate in Cycle 2 and 3 and are therefore "zero". | Posted | Number | Number subject affected | Day 84 (TV4) to Day 119 (FUV5) of cycle 2 |
|
|
|
|
| Primary | Frequency of Subjects With a Deterioration of Hearing Threshold at Day 203 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | Posted | Number | Number subject affected | Day 168 (TV7) up to Day 203 (FUV8) of cycle 3 |
|
|
|
| Secondary | Frequency of Subjects With a Deterioration of Hearing Threshold at Day 84 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available. | Posted | Number | Number subject affected | Day 1 (TV1) to Day 84 (FUV3) of cycle 1 |
|
|
|
|
| Secondary | Frequency of Subjects With a Deterioration of Hearing Threshold at Day 168 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available. | Posted | Number | Number subject affected | Day 84 (TV4) to Day 168 (FUV6) of cycle 2 |
|
|
|
|
| Secondary | Frequency of Subjects With a Deterioration of Hearing Threshold at Day 252 (Air Conduction) | Valid for Safety Analysis Set was used. Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound. The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies. | The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available. | Posted | Number | Number subject affected | Day 168 (TV7) to Day 252 (FUV9) of cycle 3 |
|
|
|
| 2 |
| 114 |
| 25 |
| 114 |
| EG001 | 2 Cycles AM-101 | Subjects that participated in 2 treatment cycles of the AMPACT1 study, received 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0 - D4) in cycle 1 and after final follow-up (D84) of cycle 1, they rolled-over to treatment cycle 2 receiving once more 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D84 - D88). | 1 | 67 | 25 | 67 |
| EG002 | 3 Cycles AM-101 | Subjects that participated in all 3 treatment cycles of the AMPACT1 study, received 3 x 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days. The subjects could only roll-over if they completed the final follow-up of the previous cycle and were still eligible. In cycle 1 treatment was within D0 - D4. Cycle 2 treatment within D84 - D88. And treatment for cycle 3 within D168-D172. Final follow-up after 3 treatment cycles was FUV9 (D252). | 1 | 76 | 37 | 76 |
| Lip and/or oral cavity cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Systematic Assessment |
|
| Adnexa uteri cyst | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Adnexa uteri mass | Reproductive system and breast disorders | MedDRA (19.0) | Systematic Assessment |
|
| Osteonecrosis | Musculoskeletal and connective tissue 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 |
|
| Otorrhoea | 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 |
|
| Influenza | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Eustachian tube dysfunction | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hyperacusis | Ear and labyrinth disorders | MedDRA (19.0) | Systematic Assessment |
|
| Bronchitis | 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 |
|
| Dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Artificial crown procedure | Surgical and medical procedures | 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 |
| Superiority |
| Fisher Exact | 0.1001 | Superiority |