Trial Outcomes & Findings for AM-101 in the Treatment of Acute Tinnitus 2 (NCT NCT01803646)

Last Updated: 2018-05-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

343 participants

Primary outcome timeframe

Screening (D-14) versus final follow-up (D83)

Results posted on

2018-05-29

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	AM-101 0.87 mg/mL Gel Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel Three intratympanic administration of placebo gel within 5 days (D0-D4).
Overall Study STARTED	204	139
Overall Study COMPLETED	187	129
Overall Study NOT COMPLETED	17	10

Reasons for withdrawal

Reasons for withdrawal
Measure	AM-101 0.87 mg/mL Gel Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel Three intratympanic administration of placebo gel within 5 days (D0-D4).
Overall Study Protocol Violation	1	0
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	9	6
Overall Study Randomization error	1	2
Overall Study Lost to Follow-up	5	1

Baseline Characteristics

AM-101 in the Treatment of Acute Tinnitus 2

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AM-101 0.87 mg/mL Gel n=204 Participants Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel n=139 Participants Three intratympanic administration of placebo gel within 5 days (D0-D4).	Total n=343 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
Age, Categorical Between 18 and 65 years	188 Participants n=5 Participants	125 Participants n=7 Participants	313 Participants n=5 Participants
Age, Categorical >=65 years	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Age, Continuous	43.4 years STANDARD_DEVIATION 14.6 • n=5 Participants	44.2 years STANDARD_DEVIATION 15.2 • n=7 Participants	43.7 years STANDARD_DEVIATION 14.8 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	37 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	161 Participants n=5 Participants	102 Participants n=7 Participants	263 Participants n=5 Participants
Region of Enrollment United States	122 participants n=5 Participants	82 participants n=7 Participants	204 participants n=5 Participants
Region of Enrollment Czechia	38 participants n=5 Participants	26 participants n=7 Participants	64 participants n=5 Participants
Region of Enrollment Canada	20 participants n=5 Participants	14 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Israel	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment South Korea	15 participants n=5 Participants	12 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Turkey	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Screening (D-14) versus final follow-up (D83)

Population: 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.

Outcome measures

Outcome measures
Measure	AM-101 0.87 mg/mL Gel n=195 Participants Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel n=129 Participants Three intratympanic administration of placebo gel within 5 days (D0-D4).
Efficacy: Change in Patient-reported Tinnitus Loudness Questionnaire (TLQ) Improvement From Baseline to Follow up Visit 3 (FUV3)	0.80 units on a scale Interval 0.51 to 1.08	0.63 units on a scale Interval 0.38 to 0.87

PRIMARY outcome

Timeframe: D0 (=TV1) versus Day 84 (=FUV3)

Population: 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.

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

Outcome measures

Outcome measures
Measure	AM-101 0.87 mg/mL Gel n=180 Participants Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel n=121 Participants Three intratympanic administration of placebo gel within 5 days (D0-D4).
Co-Primary Efficacy: Improvement in Tinnitus Functional Index (TFI) Total Score From Baseline to FUV3	10.4 units on a scale Interval 6.5 to 14.3	9.6 units on a scale Interval 5.9 to 13.3

PRIMARY outcome

Timeframe: Day 35

Population: Valid for Safety dataset was used. Of the 336 valid for safety subjects, 323 could be evaluated for this endpoint.

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.

Outcome measures

Outcome measures
Measure	AM-101 0.87 mg/mL Gel n=193 Participants Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel n=130 Participants Three intratympanic administration of placebo gel within 5 days (D0-D4).
Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2) Air conduction · Subjects with hearing deterioration	12 Participants	9 Participants
Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2) Air conduction · Subjects without hearing deterioration	181 Participants	121 Participants
Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2) Bone conduction · Subjects with hearing deterioration	3 Participants	4 Participants
Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2) Bone conduction · Subjects without hearing deterioration	190 Participants	126 Participants

Adverse Events

AM-101 0.87 mg/mL Gel

Serious events: 5 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo Gel

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AM-101 0.87 mg/mL Gel n=201 participants at risk Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel n=135 participants at risk Three intratympanic administration of placebo gel within 5 days (D0-D4).
Injury, poisoning and procedural complications Lower limb fracture	0.50% 1/201 • 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).	0.00% 0/135 • 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).
Injury, poisoning and procedural complications Tendon rupture	0.50% 1/201 • 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).	0.00% 0/135 • 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).
Cardiac disorders Atrial fibrillation	0.00% 0/201 • 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).	0.74% 1/135 • 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).
Psychiatric disorders Mental disorder	0.50% 1/201 • 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).	0.00% 0/135 • 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).
Infections and infestations Urinary tract infection	0.50% 1/201 • 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).	0.00% 0/135 • 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).
Nervous system disorders Generalised tonic-clonic seizure	0.50% 1/201 • 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).	0.00% 0/135 • 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).

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	AM-101 0.87 mg/mL Gel n=201 participants at risk Three intratympanic administration of AM-101 0.87 mg/mL gel within 5 days (D0-D4)	Placebo Gel n=135 participants at risk Three intratympanic administration of placebo gel within 5 days (D0-D4).
Nervous system disorders Dizziness	5.0% 10/201 • 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).	0.74% 1/135 • 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).
Nervous system disorders Headache	5.5% 11/201 • 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).	4.4% 6/135 • 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).
General disorders Injection site pain	2.5% 5/201 • 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).	0.74% 1/135 • 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).
Ear and labyrinth disorders Ear discomfort	7.0% 14/201 • 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).	5.9% 8/135 • 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).
Ear and labyrinth disorders Ear pain	8.0% 16/201 • 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).	7.4% 10/135 • 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).
Ear and labyrinth disorders Hypoacusis	4.0% 8/201 • 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).	3.0% 4/135 • 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).
Ear and labyrinth disorders Tinnitus	4.0% 8/201 • 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).	3.7% 5/135 • 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).
Ear and labyrinth disorders Tympanic membrane perforation	2.5% 5/201 • 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).	3.0% 4/135 • 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).
Ear and labyrinth disorders Vertigo	1.00% 2/201 • 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).	3.0% 4/135 • 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).
Psychiatric disorders Anxiety	3.5% 7/201 • 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).	0.74% 1/135 • 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).
Psychiatric disorders Insomnia	2.0% 4/201 • 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).	0.00% 0/135 • 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).
Gastrointestinal disorders Nausea	2.0% 4/201 • 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).	1.5% 2/135 • 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).
Infections and infestations Nasopharyngitis	3.0% 6/201 • 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).	3.0% 4/135 • 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).
Infections and infestations Sinusitis	2.0% 4/201 • 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).	0.00% 0/135 • 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).
Infections and infestations Upper respiratory tract infection	2.5% 5/201 • 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).	1.5% 2/135 • 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).