Trial Outcomes & Findings for AM-101 in the Treatment of Post-Acute Tinnitus 1 (NCT NCT01934010)

NCT ID: NCT01934010

Last Updated: 2018-05-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

260 participants

Primary outcome timeframe

Day 1 (TV1) to Day 35 (FUV2) of cycle 1

Results posted on

2018-05-16

Participant Flow

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.

Main Inclusion Criteria: * completion of TACTT2 study * negative pregnancy test (women of childbearing potential) * willing and able to attend the study visits during at least one treatment cycle.

Participant milestones

Participant milestones
Measure	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)	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).	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).
Overall Study STARTED	114	67	76
Overall Study COMPLETED	91	56	74
Overall Study NOT COMPLETED	23	11	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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)	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).	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).
Overall Study Adverse Event	1	1	0
Overall Study Withdrawal by Subject	15	6	2
Overall Study Lost to Follow-up	7	4	0

Baseline Characteristics

AM-101 in the Treatment of Post-Acute Tinnitus 1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 Cycle AM-101 n=114 Participants 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)	2 Cycles AM-101 n=67 Participants 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).	3 Cycles AM-101 n=76 Participants 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).	Total n=257 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	106 Participants n=5 Participants	61 Participants n=7 Participants	64 Participants n=5 Participants	231 Participants n=4 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants	26 Participants n=4 Participants
Age, Continuous	43.1 years STANDARD_DEVIATION 14.1 • n=5 Participants	44.7 years STANDARD_DEVIATION 13.9 • n=7 Participants	47.6 years STANDARD_DEVIATION 15.5 • n=5 Participants	44.8 years STANDARD_DEVIATION 14.5 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	17 Participants n=7 Participants	21 Participants n=5 Participants	63 Participants n=4 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	50 Participants n=7 Participants	55 Participants n=5 Participants	194 Participants n=4 Participants
Region of Enrollment United States	71 participants n=5 Participants	45 participants n=7 Participants	40 participants n=5 Participants	156 participants n=4 Participants
Region of Enrollment Czechia	24 participants n=5 Participants	7 participants n=7 Participants	22 participants n=5 Participants	53 participants n=4 Participants
Region of Enrollment Canada	4 participants n=5 Participants	11 participants n=7 Participants	9 participants n=5 Participants	24 participants n=4 Participants
Region of Enrollment Israel	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment South Korea	11 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	16 participants n=4 Participants
Region of Enrollment Turkey	3 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	5 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (TV1) to Day 35 (FUV2) of cycle 1

Population: 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.

Outcome measures

Outcome measures
Measure	1 Cycle AM-101 n=103 Participants Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV2.	2 Cycles AM-101 n=67 Participants Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2.	3 Cycles AM-101 n=74 Participants Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2.
Frequency of Subjects With a Deterioration of Hearing Threshold at Day 35 (Air Conduction)	10 Number subject affected	2 Number subject affected	2 Number subject affected

PRIMARY outcome

Timeframe: Day 84 (TV4) to Day 119 (FUV5) of cycle 2

Population: 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".

Outcome measures

Outcome measures
Measure	1 Cycle AM-101 n=59 Participants Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV2.	2 Cycles AM-101 n=75 Participants Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2.	3 Cycles AM-101 Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2.
Frequency of Subjects With a Deterioration of Hearing Threshold at Day 119 (Air Conduction)	1 Number subject affected	0 Number subject affected	—

PRIMARY outcome

Timeframe: Day 168 (TV7) up to Day 203 (FUV8) of cycle 3

Outcome measures

Outcome measures
Measure	1 Cycle AM-101 n=74 Participants Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV2.	2 Cycles AM-101 Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2.	3 Cycles AM-101 Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2.
Frequency of Subjects With a Deterioration of Hearing Threshold at Day 203 (Air Conduction)	2 Number subject affected	—	—

SECONDARY outcome

Timeframe: Day 1 (TV1) to Day 84 (FUV3) of cycle 1

Population: 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.

Outcome measures

Outcome measures
Measure	1 Cycle AM-101 n=91 Participants Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV2.	2 Cycles AM-101 n=66 Participants Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2.	3 Cycles AM-101 n=75 Participants Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2.
Frequency of Subjects With a Deterioration of Hearing Threshold at Day 84 (Air Conduction)	10 Number subject affected	3 Number subject affected	0 Number subject affected

SECONDARY outcome

Timeframe: Day 84 (TV4) to Day 168 (FUV6) of cycle 2

Population: 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.

Outcome measures

Outcome measures
Measure	1 Cycle AM-101 n=55 Participants Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV2.	2 Cycles AM-101 n=76 Participants Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2.	3 Cycles AM-101 Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2.
Frequency of Subjects With a Deterioration of Hearing Threshold at Day 168 (Air Conduction)	0 Number subject affected	1 Number subject affected	—

SECONDARY outcome

Timeframe: Day 168 (TV7) to Day 252 (FUV9) of cycle 3

Population: 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.

Outcome measures

Outcome measures
Measure	1 Cycle AM-101 n=74 Participants Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV2.	2 Cycles AM-101 Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2.	3 Cycles AM-101 Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2.
Frequency of Subjects With a Deterioration of Hearing Threshold at Day 252 (Air Conduction)	2 Number subject affected	—	—

Adverse Events

1 Cycle AM-101

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

2 Cycles AM-101

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

3 Cycles AM-101

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1 Cycle AM-101 n=114 participants at risk 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)	2 Cycles AM-101 n=67 participants at risk 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).	3 Cycles AM-101 n=76 participants at risk 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).
Investigations Liver function test increased	0.88% 1/114 • 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".	0.00% 0/67 • 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".	0.00% 0/76 • 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".
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip and/or oral cavity cancer	0.88% 1/114 • 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".	0.00% 0/67 • 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".	0.00% 0/76 • 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".
Reproductive system and breast disorders Adnexa uteri cyst	0.00% 0/114 • 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".	1.5% 1/67 • 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".	0.00% 0/76 • 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".
Reproductive system and breast disorders Adnexa uteri mass	0.00% 0/114 • 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".	1.5% 1/67 • 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".	0.00% 0/76 • 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".
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/114 • 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".	0.00% 0/67 • 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".	1.3% 1/76 • 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".

Other adverse events

Additional Information

Thomas Meyer, CEO

Auris Medical Inc.

Phone: +1 312 396 4150

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	1 Cycle AM-101 n=114 participants at risk 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)	2 Cycles AM-101 n=67 participants at risk 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).	3 Cycles AM-101 n=76 participants at risk 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).
Nervous system disorders Headache	4.4% 5/114 • 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".	10.4% 7/67 • 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".	11.8% 9/76 • 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".
Ear and labyrinth disorders Ear discomfort	2.6% 3/114 • 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".	13.4% 9/67 • 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".	9.2% 7/76 • 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".
Ear and labyrinth disorders Ear pain	8.8% 10/114 • 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".	19.4% 13/67 • 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".	10.5% 8/76 • 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".
Ear and labyrinth disorders Hypoacusis	4.4% 5/114 • 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".	6.0% 4/67 • 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".	5.3% 4/76 • 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".
Ear and labyrinth disorders Otorrhoea	0.88% 1/114 • 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".	6.0% 4/67 • 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".	3.9% 3/76 • 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".
Ear and labyrinth disorders Tinnitus	0.00% 0/114 • 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".	3.0% 2/67 • 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".	6.6% 5/76 • 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".
Ear and labyrinth disorders Tympanic membrane perforation	0.00% 0/114 • 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".	0.00% 0/67 • 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".	3.9% 3/76 • 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".
Ear and labyrinth disorders Vertigo	0.00% 0/114 • 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".	3.0% 2/67 • 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".	1.3% 1/76 • 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".
Infections and infestations Influenza	0.00% 0/114 • 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".	3.0% 2/67 • 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".	0.00% 0/76 • 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".
Infections and infestations Nasopharyngitis	3.5% 4/114 • 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".	3.0% 2/67 • 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".	7.9% 6/76 • 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".
Ear and labyrinth disorders Eustachian tube dysfunction	0.88% 1/114 • 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".	0.00% 0/67 • 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".	2.6% 2/76 • 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".
Ear and labyrinth disorders Hyperacusis	0.00% 0/114 • 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".	0.00% 0/67 • 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".	2.6% 2/76 • 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".
Infections and infestations Bronchitis	0.00% 0/114 • 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".	0.00% 0/67 • 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".	2.6% 2/76 • 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".
Infections and infestations Sinusitis	0.00% 0/114 • 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".	0.00% 0/67 • 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".	2.6% 2/76 • 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".
Infections and infestations Upper respiratory tract infection	0.00% 0/114 • 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".	1.5% 1/67 • 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".	2.6% 2/76 • 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".
Nervous system disorders Dizziness	0.00% 0/114 • 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".	1.5% 1/67 • 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".	2.6% 2/76 • 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".
Psychiatric disorders Anxiety	0.88% 1/114 • 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".	1.5% 1/67 • 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".	2.6% 2/76 • 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".
Surgical and medical procedures Artificial crown procedure	0.00% 0/114 • 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".	0.00% 0/67 • 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".	2.6% 2/76 • 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".