Trial Outcomes & Findings for Otoprotection With SPI-1005 for Prevention of Temporary Auditory Threshold Shift (NCT NCT01444846)

Last Updated: 2026-06-03

Results Overview

The primary efficacy analysis was change in air conduction threshold at 4 kHz collected in the ITT Population on the day of sound exposure. Baseline hearing thresholds were collected on Clinic Visit 2 prior to sound exposure and used in calculating the primary efficacy endpoints. Hearing thresholds after sound exposure were collected and compared to baseline threshold to calculate change from baseline. Threshold changes from baseline were determined for each ear, frequency, and post sound time point, then analyzed by Mixed-effects Model Repeated Measures (MMRM) methods using triply repeated measurements for each subject. The MMRM had fixed effects for treatment, ear, frequency, and time, all 2-way interactions and the 3-way interaction treatment by-frequency-by-time plus a random effect for subject nested within treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

15 minutes post Controlled Sound Challenge

Results posted on

2026-06-03

Participant Flow

Participant milestones

Participant milestones
Measure	SPI-1005 Low Dose 200mg SPI-1005, capsule, bid, po, x4d SPI-1005 Low dose: Oral capsules, 200 mg ebselen, twice daily, 4 days	SPI-1005 Middle Dose 400mg SPI-1005, capsule, bid, po, x4d SPI-1005 Middle dose: Oral capsules, 400 mg ebselen, twice daily, 4 days	SPI-1005 High Dose 600mg SPI-1005, capsule, bid, po, x4d SPI-1005 High dose: Oral capsules, 600 mg ebselen, twice daily, 4 days	Placebo 0mg SPI-1005, capsule, bid, po, x4d Placebo: Oral capsules, 0 mg ebselen, twice daily, 4 days
Overall Study STARTED	22	20	21	20
Overall Study COMPLETED	20	20	21	19
Overall Study NOT COMPLETED	2	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Otoprotection With SPI-1005 for Prevention of Temporary Auditory Threshold Shift

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SPI-1005 Low Dose n=22 Participants 200mg SPI-1005, capsule, bid, po, x4d SPI-1005 Low dose: Oral capsules, 200 mg ebselen, twice daily, 4 days	SPI-1005 Middle Dose n=20 Participants 400mg SPI-1005, capsule, bid, po, x4d SPI-1005 Middle dose: Oral capsules, 400 mg ebselen, twice daily, 4 days	SPI-1005 High Dose n=21 Participants 600mg SPI-1005, capsule, bid, po, x4d SPI-1005 High dose: Oral capsules, 600 mg ebselen, twice daily, 4 days	Placebo n=20 Participants 0mg SPI-1005, capsule, bid, po, x4d Placebo: Oral capsules, 0 mg ebselen, twice daily, 4 days	Total n=83 Participants Total of all reporting groups
Age, Customized	21.0 years n=20 Participants	20.0 years n=20 Participants	20.0 years n=40 Participants	21.0 years n=5 Participants	20.0 years n=9 Participants
Sex: Female, Male Female	10 Participants n=20 Participants	11 Participants n=20 Participants	14 Participants n=40 Participants	13 Participants n=5 Participants	48 Participants n=9 Participants
Sex: Female, Male Male	12 Participants n=20 Participants	9 Participants n=20 Participants	7 Participants n=40 Participants	7 Participants n=5 Participants	35 Participants n=9 Participants
Region of Enrollment United States	22 participants n=20 Participants	20 participants n=20 Participants	21 participants n=40 Participants	20 participants n=5 Participants	83 participants n=9 Participants

PRIMARY outcome

Timeframe: 15 minutes post Controlled Sound Challenge

Population: Intent To Treat (ITT) Population

Outcome measures

Outcome measures
Measure	SPI-1005 Low Dose n=40 Ears 200mg SPI-1005, capsule, bid, po, x4d SPI-1005 Low dose: Oral capsules, 200 mg ebselen, twice daily, 4 days	SPI-1005 Middle Dose n=40 Ears 400mg SPI-1005, capsule, bid, po, x4d SPI-1005 Middle dose: Oral capsules, 400 mg ebselen, twice daily, 4 days	SPI-1005 High Dose n=42 Ears 600mg SPI-1005, capsule, bid, po, x4d SPI-1005 High dose: Oral capsules, 600 mg ebselen, twice daily, 4 days	Placebo n=40 Ears 0mg SPI-1005, capsule, bid, po, x4d Placebo: Oral capsules, 0 mg ebselen, twice daily, 4 days
Change in Temporary Threshold Shift at 4 kHz--Intent To Treat (ITT) Population	3.23 dbHL Interval 1.97 to 4.49	1.32 dbHL Interval 0.06 to 2.58	3.81 dbHL Interval 2.57 to 5.04	4.07 dbHL Interval 2.81 to 5.34

PRIMARY outcome

Timeframe: 15 minutes post Controlled Sound Challenge

Population: Analysis of the Per Protocol population includes all subjects (n=77) that were noise exposed, and completed the protocol as directed.

The primary efficacy analysis was change in air conduction threshold at 4 kHz collected in the PP Population on the day of sound exposure. Baseline hearing thresholds were collected on Clinic Visit 2 prior to sound exposure and used in calculating the primary efficacy endpoints. Hearing thresholds after sound exposure were collected and compared to baseline threshold to calculate change from baseline. Threshold changes from baseline were determined for each ear, frequency, and post sound time point, then analyzed by Mixed-effects Model Repeated Measures (MMRM) methods using triply repeated measurements for each subject. The MMRM had fixed effects for treatment, ear, frequency, and time, all 2-way interactions and the 3-way interaction treatment by-frequency-by-time plus a random effect for subject nested within treatment.

Outcome measures

Outcome measures
Measure	SPI-1005 Low Dose n=19 Participants 200mg SPI-1005, capsule, bid, po, x4d SPI-1005 Low dose: Oral capsules, 200 mg ebselen, twice daily, 4 days	SPI-1005 Middle Dose n=20 Participants 400mg SPI-1005, capsule, bid, po, x4d SPI-1005 Middle dose: Oral capsules, 400 mg ebselen, twice daily, 4 days	SPI-1005 High Dose n=18 Participants 600mg SPI-1005, capsule, bid, po, x4d SPI-1005 High dose: Oral capsules, 600 mg ebselen, twice daily, 4 days	Placebo n=20 Participants 0mg SPI-1005, capsule, bid, po, x4d Placebo: Oral capsules, 0 mg ebselen, twice daily, 4 days
Change in Temporary Threshold Shift at 4 kHz--Per Protocol (PP) Population	3.35 dB HL Interval 2.07 to 4.64	1.30 dB HL Interval 0.05 to 2.55	3.69 dB HL Interval 2.37 to 5.01	4.09 dB HL Interval 2.84 to 5.35

Adverse Events

SPI-1005 Low Dose

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

SPI-1005 Middle Dose

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

SPI-1005 High Dose

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Jonathan Kil, Chief Medical Officer

SOUND PHARMACEUTICALS, INC.

Phone: 2066342559

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Other adverse events
Measure	SPI-1005 Low Dose n=22 participants at risk 200mg SPI-1005, capsule, bid, po, x4d SPI-1005 Low dose: Oral capsules, 200 mg ebselen, twice daily, 4 days	SPI-1005 Middle Dose n=20 participants at risk 400mg SPI-1005, capsule, bid, po, x4d SPI-1005 Middle dose: Oral capsules, 400 mg ebselen, twice daily, 4 days	SPI-1005 High Dose n=21 participants at risk 600mg SPI-1005, capsule, bid, po, x4d SPI-1005 High dose: Oral capsules, 600 mg ebselen, twice daily, 4 days	Placebo n=20 participants at risk 0mg SPI-1005, capsule, bid, po, x4d Placebo: Oral capsules, 0 mg ebselen, twice daily, 4 days
Ear and labyrinth disorders Hypoacusis	4.5% 1/22 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	4.8% 1/21 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Injury, poisoning and procedural complications Procedural dizziness	4.5% 1/22 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Injury, poisoning and procedural complications Sunburn	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Investigations Blood alkaline phosphatase increased	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	4.8% 1/21 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Investigations Blood phosphorus increased	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Investigations Haemoglobin decreased	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	4.8% 1/21 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Investigations White blood cell count decreased	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	4.8% 1/21 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Nervous system disorders Dizziness	4.5% 1/22 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Nervous system disorders Headache	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Nervous system disorders Nystagmus	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	4.8% 1/21 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	9.5% 2/21 • Number of events 2 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.
Vascular disorders Hot flush	0.00% 0/22 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	5.0% 1/20 • Number of events 1 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/21 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.	0.00% 0/20 • AEs were collected over a period of roughly 1 year. University of Florida clinics collect all changes in AE condition as separate AEs. If an AE that was reported during the study changed in severity or frequency, that AE was given a stop date/time and another AE was recorded in the database with a start date/time that matched the stop date/time of the original AE. If the AE changed again, another AE was recorded in the database with a start date/time that matched the previous AE record.