Trial Outcomes & Findings for Study of OTO-104 in Subjects With Unilateral Meniere's Disease (NCT NCT02717442)

Last Updated: 2023-01-13

Results Overview

In the Full Analysis Set (FAS)-1 population, the number of DVDs at Week 12 (the 4-week \[28 days\] interval from Week 9 through Week 12) was compared between OTO-104 and placebo. Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

176 participants

Primary outcome timeframe

3 months

Results posted on

2023-01-13

Participant Flow

176 subjects were randomized and 174 subjects received study drug. The most common reason for screen failure was insufficient number of definitive vertigo days in the 28-day lead-in period. The first subject enrolled March 21, 2016, and the last subject completed September 15, 2017. A total of 49 centers in Europe (Belgium, France, Germany, Italy, Poland, United Kingdom) enrolled subjects.

This study was terminated early based on results of study 104-201506, a US Phase 3 study that indicated no statistically significant difference in the primary endpoint of reduction in definitive vertigo days (DVD) for OTO-104 vs placebo nor for any of the secondary endpoints. Decision was made to terminate all ongoing studies on August 31, 2017, including this study. At the time of termination, 112/176 randomized subjects completed the study out to Week 12 (Month 3).

Participant milestones

Participant milestones
Measure	OTO-104 12 mg dexamethasone OTO-104: Single intratympanic injection of 12 mg OTO-104	Placebo Placebo: Single intratympanic injection of placebo
Overall Study STARTED	88	88
Overall Study COMPLETED	53	59
Overall Study NOT COMPLETED	35	29

Reasons for withdrawal

Reasons for withdrawal
Measure	OTO-104 12 mg dexamethasone OTO-104: Single intratympanic injection of 12 mg OTO-104	Placebo Placebo: Single intratympanic injection of placebo
Overall Study Study Terminated by Sponsor	31	29
Overall Study Subject Randomized, but Did not Receive Drug	2	0
Overall Study Other - Not Specified	2	0

Baseline Characteristics

Study of OTO-104 in Subjects With Unilateral Meniere's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OTO-104 (Full Analysis Set -1) n=86 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=88 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement(i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least1 post baseline daily diary entry).	Total n=174 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	72 Participants n=5 Participants	75 Participants n=7 Participants	147 Participants n=5 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Age, Continuous	53.0 years n=5 Participants	53.0 years n=7 Participants	53.0 years n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	48 Participants n=7 Participants	92 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	40 Participants n=7 Participants	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	75 Participants n=7 Participants	152 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	82 Participants n=5 Participants	82 Participants n=7 Participants	164 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Belgium	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment France	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Germany	13 participants n=5 Participants	15 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Italy	12 participants n=5 Participants	6 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Poland	28 participants n=5 Participants	34 participants n=7 Participants	62 participants n=5 Participants
Region of Enrollment United Kingdom	26 participants n=5 Participants	23 participants n=7 Participants	49 participants n=5 Participants
Previous IT Steroid Injection	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Population: A subject is included in the analysis if they received study drug, had a baseline definitive vertigo measurement for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline, i.e., at least one post-baseline daily diary entry. The model and corresponding method of estimation adjusted for overdispersion and addressed missing 4-week intervals under the assumption of Missing at Random (MAR).

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=86 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=88 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-1 Population	2.336 Definitive Vertigo Day Interval 1.747 to 3.125	3.549 Definitive Vertigo Day Interval 2.763 to 4.56

PRIMARY outcome

Timeframe: 3 months

Population: The FAS - 2 includes all subjects from FAS-1 who were randomized 12 weeks prior to the study termination decision date of August 31, 2017 (i.e., subjects that had the opportunity to complete 12 weeks of daily diary entries in the study at the time of study termination).

The number of DVDs at Week 12 (the 4-week \[28 days\] interval from Week 9 through Week 12) was compared between OTO-104 and placebo. Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=55 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=56 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-2 Population	2.044 Definitive Vertigo Day Interval 1.48 to 2.822	3.467 Definitive Vertigo Day Interval 2.617 to 4.594

SECONDARY outcome

Timeframe: 3 months

Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in. Questionnaire - subjects were instructed to record the effect on their daily activities of their total vertigo experienced that day using a 5-point scoring system: 0 = normal activity 1. = slight limitation 2. = moderate limitation 3. = sick at home 4. = bedridden

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=86 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=88 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
Effect of Vertigo on Daily Activities - Number of Days Sick at Home or Bedridden at Week 12 (Month 3): FAS-1	1.2 days Standard Deviation 2.32	2.3 days Standard Deviation 4.58

SECONDARY outcome

Timeframe: 3 months

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=55 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=56 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
Effect of Vertigo on Daily Activities - Number of Days Sick at Home or Bedridden at Week 12 (Month 3): FAS-2	1.2 days Standard Deviation 2.18	2.2 days Standard Deviation 4.68

SECONDARY outcome

Timeframe: 3 months

Population: Only subjects that had a Month 3 otoscopic examination are included in assessment of this emdpoint.

Otoscopic examinations were conducted at each visit. It was considered important to understand if the tympanic perforation that resulted from the IT injection at the Baseline visit persisted at the end of study visit (Week12 \[Month 3\]). Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=53 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=59 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
Otoscopic Examination - Tympanic Membrane Perforation at Week 12 (Month 3)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 3 Months

Population: Subjects that had no impairment at the baseline visit (air-bone gap \<=10 dB) and had an audiogram collected at the Week 12 (Month 3) visit.

The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment (\<=10 dB) to impairment (\>10 dB) when measure at 500 Hz. Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=48 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=52 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
Audiometry - Shift in Air-Bone Gap at 500 Hz From Baseline to Week 12 (Month 3)	8 Participants	7 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Subjects that had no impairment at the baseline visit (air-bone gap \<=10 dB) and had an audiogram collected at the Week 12 (Month 3) visit.

The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 1000 Hz. Week 12 (Month 3) = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=39 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=45 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3)	11 Participants	3 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Subjects that had no impairment at the baseline visit (air-bone gap \<=10 dB) and had an audiogram collected at the Week 12 (Month 3) visit.

The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 2000 Hz. Week 12 (Month 3) = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.

Outcome measures

Outcome measures
Measure	OTO-104 (Full Analysis Set -1) n=42 Participants Subjects that were randomized to OTO-104, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).	Placebo (Full Analysis Set - 1) n=51 Participants Subjects that were randomized to placebo, received study drug, had a baseline definitive vertigo measurement (i.e., at least 1 baseline daily diary entry) for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline (i.e., at least 1 post baseline daily diary entry).
Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3)	0 Participants	4 Participants

Adverse Events

OTO-104 (Safety Analysis Set)

Serious events: 2 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo (Safety Analysis Set)

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OTO-104 (Safety Analysis Set) n=86 participants at risk All subjects who receivedOTO-104. Subjects were included in this treatment group according to the actual treatment received regardless of their randomized assignment.	Placebo (Safety Analysis Set) n=88 participants at risk All subjects who received Placebo. Subjects were included in this treatment group according to the actual treatment received regardless of their randomized assignment.
Injury, poisoning and procedural complications Head Injury	1.2% 1/86 • Number of events 1 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	0.00% 0/88 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Hepatobiliary disorders Cholecystitis	1.2% 1/86 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	0.00% 0/88 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.

Other adverse events

Additional Information

Otonomy Medical Information Center

Otonomy, Inc.

Phone: 1-844-686-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	OTO-104 (Safety Analysis Set) n=86 participants at risk All subjects who receivedOTO-104. Subjects were included in this treatment group according to the actual treatment received regardless of their randomized assignment.	Placebo (Safety Analysis Set) n=88 participants at risk All subjects who received Placebo. Subjects were included in this treatment group according to the actual treatment received regardless of their randomized assignment.
Nervous system disorders Headache	10.5% 9/86 • Number of events 86 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	8.0% 7/88 • Number of events 88 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Nervous system disorders Dizziness	8.1% 7/86 • Number of events 7 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	4.5% 4/88 • Number of events 4 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Nervous system disorders Dysgeusia	3.5% 3/86 • Number of events 3 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	2.3% 2/88 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Nervous system disorders Hypoesthesia	2.3% 2/86 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	0.00% 0/88 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Ear and labyrinth disorders Meniere's Disease	5.8% 5/86 • Number of events 5 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	1.1% 1/88 • Number of events 1 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Ear and labyrinth disorders Tinnitus	4.7% 4/86 • Number of events 4 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	2.3% 2/88 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Ear and labyrinth disorders Ear Pain	3.5% 3/86 • Number of events 3 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	3.4% 3/88 • Number of events 3 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Ear and labyrinth disorders Vertigo	3.5% 3/86 • Number of events 3 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	2.3% 2/88 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Ear and labyrinth disorders Ear Discomfort	2.3% 2/86 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	2.3% 2/88 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Infections and infestations Nasopharyngitis	2.3% 2/86 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	3.4% 3/88 • Number of events 3 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Infections and infestations Upper Respiratory Tract Infection	2.3% 2/86 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	0.00% 0/88 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Gastrointestinal disorders Nausea	3.5% 3/86 • Number of events 3 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	2.3% 2/88 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Skin and subcutaneous tissue disorders Erythema	2.3% 2/86 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	0.00% 0/88 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
General disorders Injection Site Pain	2.3% 2/86 • Number of events 2 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	0.00% 0/88 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.
Psychiatric disorders Suicidal Ideation	3.5% 3/86 • Number of events 3 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.	1.1% 1/88 • Number of events 1 • Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.