Trial Outcomes & Findings for A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye (NCT NCT03982368)

NCT ID: NCT03982368

Last Updated: 2024-04-19

Results Overview

The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes) Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 261 participants
• Primary outcome timeframe: Baseline, week 4
• Results posted on: 2024-04-19

Participant Flow

Enrollment of a total of 300 patients was planned. Due to restrictions in the hospital clinical routines related to coronavirus disease 2019, the sponsor decided to prematurely stop enrollment in the study in order to comply with quarantine measures of each country and avoid risks of infection of COVID-19 illness for all involved patients. A total of 261 patients were randomized to receive study treatment: 87 in the rhNGF TID group, 86 in the rhNGF BID group, and 88 in the vehicle TID group.

Participant milestones

Measure	rhNGF 20 μg/ml TID One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Overall Study STARTED	87	86	88
Overall Study FAS Popuation	81	82	84
Overall Study PP Population	72	71	80
Overall Study COMPLETED	74	79	83
Overall Study NOT COMPLETED	13	7	5

Reasons for withdrawal

Measure	rhNGF 20 μg/ml TID One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Overall Study Adverse Event	6	4	3
Overall Study Lost to Follow-up	2	1	0
Overall Study Withdrawal by Subject	1	2	0
Overall Study unknow	4	0	2

Baseline Characteristics

A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye

Baseline characteristics by cohort

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)	Total n=247 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	51 Participants n=5 Participants	54 Participants n=7 Participants	61 Participants n=5 Participants	166 Participants n=4 Participants
Age, Categorical >=65 years	30 Participants n=5 Participants	28 Participants n=7 Participants	23 Participants n=5 Participants	81 Participants n=4 Participants
Age, Continuous	62.0 years STANDARD_DEVIATION 13.52 • n=5 Participants	60.2 years STANDARD_DEVIATION 12.39 • n=7 Participants	59.1 years STANDARD_DEVIATION 11.50 • n=5 Participants	60.4 years STANDARD_DEVIATION 12.49 • n=4 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	69 Participants n=7 Participants	72 Participants n=5 Participants	198 Participants n=4 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	49 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants	37 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=5 Participants	73 Participants n=7 Participants	71 Participants n=5 Participants	210 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	81 participants n=5 Participants	82 participants n=7 Participants	84 participants n=5 Participants	247 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, week 4

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye.

Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.

The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes)

Cutoff values:

<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Full Analysis Set	2.60 mm Standard Error 0.77	3.99 mm Standard Error 0.76	1.68 mm Standard Error 0.75

PRIMARY outcome

Timeframe: Baseline, week 4

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

The Schirmer test is used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye.

Without previously instilling anesthetic drops, the Schirmer strip is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.

The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes)

Cutoff values:

<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Schirmer I Test (Without Anesthesia) vs Week 4 - Per Protocol Set	2.99 mm Standard Error 0.78	3.72 mm Standard Error 0.79	1.28 mm Standard Error 0.74

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Full Analysis Set	-24.6 score on a scale Standard Deviation 27.15	-20.3 score on a scale Standard Deviation 24.91	-22.2 score on a scale Standard Deviation 22.29

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The global score is calculated by taking the square root of the product of the severity of symptoms per the frequency of symptoms. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Severity vs Week 4 - Per Protocol Set	-24.9 score on a scale Standard Deviation 27.35	-19.9 score on a scale Standard Deviation 25.34	-22.1 score on a scale Standard Deviation 21.74

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome.The SANDE global score is calculated by taking the square root of the product of the frequency of symptoms and the severity of symptoms. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Full Analysis Set	-24.9 score on a scale Standard Deviation 26.29	-22.7 score on a scale Standard Deviation 25.42	-24.0 score on a scale Standard Deviation 23.81

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

The SANDE (symptom assessment in dry eye) score is composed by two questions presented in visual analog scale. The two questions assess the frequency and severity of dry eye syndrome. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Symptoms Questionnaire (SANDE) Scores for Frequency vs Week 4 - Per Protocol Set	-24.7 score on a scale Standard Deviation 26.73	-22.2 score on a scale Standard Deviation 25.67	-23.8 score on a scale Standard Deviation 23.92

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips.

Cut-off values:

<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Full Analysis Set	2.19 mm Standard Error 0.69	0.89 mm Standard Error 0.69	0.21 mm Standard Error 0.68

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes.

All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips.

Cut-off values:

<5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Schirmer II Test (With Anesthesia) vs Week 4 - Per Protocol Set	2.24 mm Standard Error 0.69	0.54 mm Standard Error 0.70	-0.18 mm Standard Error 0.66

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome.

The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome.

Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set corneal and conjunctival total score	-3.75 score on a scale Standard Error 0.63	-2.95 score on a scale Standard Error 0.62	-2.60 score on a scale Standard Error 0.61
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set corneal score	-1.9 score on a scale Standard Error 2.84	-1.8 score on a scale Standard Error 2.72	-1.5 score on a scale Standard Error 2.92
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Full Analysis Set conjunctiva score	-2.1 score on a scale Standard Error 3.17	-1.2 score on a scale Standard Error 3.58	-1.4 score on a scale Standard Error 3.36

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results. This analysis set was used for supportive efficacy analysis.

Corneal staining total score is defined as the sum of scores from 5 corneal areas: Central, Superior, Temporal, Nasal, and Inferior. The score for each area ranges from 0 to 3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage. Thus, the corneal staining total score can range from 0 to 15 where the higher the score the worse is the outcome.

The conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area and a peripheral area with a grading scale of 0-3 where grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage and with a maximal score of 9 for the nasal and temporal conjunctiva. Thus, the conjunctival staining total score can range from 0 to 18 where the higher the score the worse is the outcome.

Corneal and conjunctiva vital staining total score is the sum of corneal staining total score and conjunctiva total score.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set Total score	-3.94 score on a scale Standard Error 0.60	-2.61 score on a scale Standard Error 0.61	-2.40 score on a scale Standard Error 0.57
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set Corneal score	-1.9 score on a scale Standard Error 2.80	-1.8 score on a scale Standard Error 2.61	-1.5 score on a scale Standard Error 2.85
Change From Baseline in Corneal and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) vs Week 4 - Per Protocol Set Conjunctival score	-1.9 score on a scale Standard Error 2.95	-1.0 score on a scale Standard Error 3.05	-1.3 score on a scale Standard Error 3.32

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is performed after instillation of 5 μL of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient is instructed to blink several times to thoroughly mix the fluorescein with the tear film.

A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Full Analysis Set	1.11 seconds Standard Error 0.25	0.43 seconds Standard Error 0.25	0.15 seconds Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, week 4

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

Tear film break-up time (TFBUT) is the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement is an easy and fast method used to assess the stability of tear film. It is a standard diagnostic procedure in the dry eye clinics. TFBUT is measured by determining the time to tear break-up. The TFBUT is performed after instillation of 5 μL of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient is instructed to blink several times to thoroughly mix the fluorescein with the tear film.

A TFBUT greater than 15 seconds is considered normal, while a break time of less than 10 seconds is to be considered pathological.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Tear Film Break-Up Time (TFBUT) vs Week 4 - Per Protocol Set	1.11 seconds Standard Error 0.27	0.47 seconds Standard Error 0.27	0.19 seconds Standard Error 0.25

SECONDARY outcome

Timeframe: At week 4

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

The SANDE score is calculated by taking the square root of the product of the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage.

The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15.

Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18).

Briefly, grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Full Analysis Set	2 Participants	9 Participants	3 Participants

SECONDARY outcome

Timeframe: At week 4

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

The SANDE score is calculated by taking the square root of the product of the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage.

The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15.

Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18).

Briefly, grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Number of Patients Who Experienced a Worsening in Symptom Scores (SANDE) and/or NEI Score ≥ 50% Assessed at Week 4 - Per Protocol Set	0 Participants	8 Participants	3 Participants

SECONDARY outcome

Timeframe: At weeks 4, 8, 12 and 16

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye.

The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions.

1. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items.

2. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops.

3. The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother.

Scores for each dimensions ranged from 0 to 100.

Higher scores for:

• dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities;
• symptom-bother dimension indicates greater bother due to symptoms;
• satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness;
• treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Daily activity limitations - Chance from baseline to week 4	16.5 score on a scale Standard Deviation 20.71	19.5 score on a scale Standard Deviation 17.55	13.1 score on a scale Standard Deviation 20.60
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Daily activity limitations - Chance from baseline to week 8	16.8 score on a scale Standard Deviation 23.49	14.8 score on a scale Standard Deviation 18.07	11.2 score on a scale Standard Deviation 17.54
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Daily activity limitations - Chance from baseline to week 12	15.7 score on a scale Standard Deviation 21.10	15.5 score on a scale Standard Deviation 20.01	11.1 score on a scale Standard Deviation 17.45
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Daily activity limitations - Chance from baseline to week 16	14.2 score on a scale Standard Deviation 20.05	14.4 score on a scale Standard Deviation 21.23	9.4 score on a scale Standard Deviation 16.74
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Emotional well-being - change from baseline to week 4	14.5 score on a scale Standard Deviation 21.18	16.3 score on a scale Standard Deviation 20.40	15.0 score on a scale Standard Deviation 20.47
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Emotional well-being - change from baseline to week 8	16.2 score on a scale Standard Deviation 21.33	13.4 score on a scale Standard Deviation 18.64	12.7 score on a scale Standard Deviation 17.69
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Emotional well-being - change from baseline to week 12	14.2 score on a scale Standard Deviation 18.66	15.3 score on a scale Standard Deviation 17.95	14.2 score on a scale Standard Deviation 18.20
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Emotional well-being - change from baseline to week 16	16.0 score on a scale Standard Deviation 18.54	15.5 score on a scale Standard Deviation 19.17	13.5 score on a scale Standard Deviation 20.22
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set work limitations - change from baseline to week 4	16.3 score on a scale Standard Deviation 27.13	20.6 score on a scale Standard Deviation 24.29	17.4 score on a scale Standard Deviation 24.09
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set work limitations - change from baseline to week 8	18.0 score on a scale Standard Deviation 24.94	18.3 score on a scale Standard Deviation 19.00	17.0 score on a scale Standard Deviation 22.52
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set work limitations - change from baseline to week 12	16.4 score on a scale Standard Deviation 22.39	20.9 score on a scale Standard Deviation 22.05	17.8 score on a scale Standard Deviation 22.35
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set work limitations - change from baseline to week 16	16.3 score on a scale Standard Deviation 20.75	20.9 score on a scale Standard Deviation 20.83	16.0 score on a scale Standard Deviation 21.63
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Treatment satisfaction/happiness - change from baseline to week 4	24.1 score on a scale Standard Deviation 30.81	19.0 score on a scale Standard Deviation 30.57	24.1 score on a scale Standard Deviation 33.57
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Treatment satisfaction/happiness - change from baseline to week 8	28.8 score on a scale Standard Deviation 28.56	19.1 score on a scale Standard Deviation 26.90	13.3 score on a scale Standard Deviation 30.69
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Treatment satisfaction/happiness - change from baseline to week 12	26.1 score on a scale Standard Deviation 30.30	19.1 score on a scale Standard Deviation 27.86	15.0 score on a scale Standard Deviation 26.83
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Treatment satisfaction/happiness - change from baseline to week 16	26.1 score on a scale Standard Deviation 26.62	23.5 score on a scale Standard Deviation 29.29	12.7 score on a scale Standard Deviation 27.03
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set treatment-related bother - change from baseline to week 4	14.6 score on a scale Standard Deviation 22.78	16.8 score on a scale Standard Deviation 25.00	13.8 score on a scale Standard Deviation 27.19
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set treatment-related bother - change from baseline to week 8	10.6 score on a scale Standard Deviation 20.61	6.5 score on a scale Standard Deviation 26.56	4.8 score on a scale Standard Deviation 26.59
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set treatment-related bother - change from baseline to week 12	10.3 score on a scale Standard Deviation 22.71	8.7 score on a scale Standard Deviation 24.91	9.0 score on a scale Standard Deviation 27.95
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set treatment-related bother - change from baseline to week 16	10.8 score on a scale Standard Deviation 20.65	8.1 score on a scale Standard Deviation 23.88	10.0 score on a scale Standard Deviation 27.14
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Dry eye symptom bother - change from baseline to week 4	-16.8 score on a scale Standard Deviation 17.80	-17.7 score on a scale Standard Deviation 16.54	-16.5 score on a scale Standard Deviation 17.04
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Dry eye symptom bother - change from baseline to week 8	-21.2 score on a scale Standard Deviation 19.56	-16.6 score on a scale Standard Deviation 15.46	-13.5 score on a scale Standard Deviation 15.01
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Dry eye symptom bother - change from baseline to week 12	-19.6 score on a scale Standard Deviation 17.41	-18.2 score on a scale Standard Deviation 17.30	-13.0 score on a scale Standard Deviation 13.01
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Full Analysis Set Dry eye symptom bother - change from baseline to week 16	-19.9 score on a scale Standard Deviation 15.62	-19.1 score on a scale Standard Deviation 17.75	-11.1 score on a scale Standard Deviation 14.46

SECONDARY outcome

Timeframe: At weeks 4, 8, 12 and 16

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye.

The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions.

1. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items.

2. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops.

3. The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother.

Scores for each dimensions ranged from 0 to 100.

Higher scores for:

• dimension of the Dry Eye Impact on Daily Life module indicates less impact on daily activities;
• symptom-bother dimension indicates greater bother due to symptoms;
• satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness;
• treatment-related bother/inconvenience indicates less treatment-related bother or inconvenience.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Daily activity limitations - Change from baseline to week 4	16.8 score on a scale Standard Deviation 21.20	19.7 score on a scale Standard Deviation 17.58	13.0 score on a scale Standard Deviation 20.63
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Daily activity limitations - Change from baseline to week 8	17.1 score on a scale Standard Deviation 23.93	15.3 score on a scale Standard Deviation 16.85	11.5 score on a scale Standard Deviation 17.47
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Daily activity limitations - Change from baseline to week 12	17.0 score on a scale Standard Deviation 20.30	16.5 score on a scale Standard Deviation 18.45	11.2 score on a scale Standard Deviation 17.64
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Daily activity limitations - Change from baseline to week 16	13.9 score on a scale Standard Deviation 19.33	15.8 score on a scale Standard Deviation 19.74	9.4 score on a scale Standard Deviation 16.94
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Emotional well-being - change from baseline to week 4	15.2 score on a scale Standard Deviation 21.73	17.3 score on a scale Standard Deviation 20.33	15.8 score on a scale Standard Deviation 20.60
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Emotional well-being - change from baseline to week 8	16.9 score on a scale Standard Deviation 21.70	13.9 score on a scale Standard Deviation 18.34	13.2 score on a scale Standard Deviation 17.55
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Emotional well-being - change from baseline to week 12	15.1 score on a scale Standard Deviation 18.58	16.4 score on a scale Standard Deviation 16.87	14.7 score on a scale Standard Deviation 18.14
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Emotional well-being - change from baseline to week 16	16.8 score on a scale Standard Deviation 18.48	16.6 score on a scale Standard Deviation 18.59	14.2 score on a scale Standard Deviation 20.11
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set work limitations - change from baseline to week 4	16.0 score on a scale Standard Deviation 27.48	21.3 score on a scale Standard Deviation 24.83	18.4 score on a scale Standard Deviation 24.23
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set work limitations - change from baseline to week 8	17.4 score on a scale Standard Deviation 25.13	18.3 score on a scale Standard Deviation 19.43	17.9 score on a scale Standard Deviation 22.29
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set work limitations - change from baseline to week 12	15.0 score on a scale Standard Deviation 21.67	21.9 score on a scale Standard Deviation 21.82	18.6 score on a scale Standard Deviation 22.14
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set work limitations - change from baseline to week 16	15.4 score on a scale Standard Deviation 19.43	21.9 score on a scale Standard Deviation 20.93	16.7 score on a scale Standard Deviation 21.80
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Treatment satisfaction/happiness - change from baseline to week 4	25.4 score on a scale Standard Deviation 31.05	19.6 score on a scale Standard Deviation 31.26	25.2 score on a scale Standard Deviation 33.81
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Treatment satisfaction/happiness - change from baseline to week 8	30.1 score on a scale Standard Deviation 28.47	21.0 score on a scale Standard Deviation 27.85	13.9 score on a scale Standard Deviation 30.66
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Treatment satisfaction/happiness - change from baseline to week 12	25.8 score on a scale Standard Deviation 31.16	21.6 score on a scale Standard Deviation 27.82	15.5 score on a scale Standard Deviation 26.81
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Treatment satisfaction/happiness - change from baseline to week 16	26.0 score on a scale Standard Deviation 27.60	24.3 score on a scale Standard Deviation 28.26	13.2 score on a scale Standard Deviation 27.18
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set treatment-related bother - change from baseline to week 4	15.7 score on a scale Standard Deviation 22.66	15.3 score on a scale Standard Deviation 23.39	14.4 score on a scale Standard Deviation 27.71
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set treatment-related bother - change from baseline to week 8	11.6 score on a scale Standard Deviation 20.73	6.9 score on a scale Standard Deviation 25.46	4.6 score on a scale Standard Deviation 26.78
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set treatment-related bother - change from baseline to week 12	9.9 score on a scale Standard Deviation 22.83	10.0 score on a scale Standard Deviation 23.05	8.7 score on a scale Standard Deviation 28.26
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set treatment-related bother - change from baseline to week 16	11.4 score on a scale Standard Deviation 20.90	9.5 score on a scale Standard Deviation 21.62	9.8 score on a scale Standard Deviation 27.51
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Dry eye symptom bother - change from baseline to week 4	-17.3 score on a scale Standard Deviation 17.19	-18.7 score on a scale Standard Deviation 16.64	-17.2 score on a scale Standard Deviation 17.10
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Dry eye symptom bother - change from baseline to week 8	-21.5 score on a scale Standard Deviation 18.88	-17.6 score on a scale Standard Deviation 15.40	-13.9 score on a scale Standard Deviation 14.97
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Dry eye symptom bother - change from baseline to week 12	-19.6 score on a scale Standard Deviation 17.41	-19.7 score on a scale Standard Deviation 17.16	-13.2 score on a scale Standard Deviation 13.18
Change From Baseline in Quality of Life (Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire vs Different Timepoints - Per Protocol Set Dry eye symptom bother - change from baseline to week 16	-20.6 score on a scale Standard Deviation 15.21	-20.7 score on a scale Standard Deviation 17.66	-11.3 score on a scale Standard Deviation 14.61

SECONDARY outcome

Timeframe: At baseline and weeks 4, 8, 12 and 16

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Patient Global Impression of Change (PGIC) - Full Analysis Set week 12 - minimally worse	5 participants	1 participants	0 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 12 - much worse	2 participants	2 participants	2 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 12 - very much worse	2 participants	1 participants	0 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 16 - very much improved	7 participants	3 participants	6 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 16 - much improved	24 participants	19 participants	16 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 16 - minimally improved	22 participants	20 participants	19 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 16 - no change	19 participants	33 participants	36 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 4 - Very Much Improved	11 participants	2 participants	4 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 4 - Much Improved	18 participants	15 participants	20 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 4 - Minimally improved	18 participants	21 participants	20 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 4 - no change	24 participants	38 participants	38 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 4 - minimally worse	6 participants	4 participants	2 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 4 - much worse	1 participants	1 participants	0 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 4 - very much worse	0 participants	0 participants	0 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 8 - Very much improved	9 participants	3 participants	1 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 8 - much improved	23 participants	11 participants	16 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 8 - minimally improved	19 participants	21 participants	17 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 8 - no change	21 participants	37 participants	46 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 8 - minimally worse	1 participants	4 participants	2 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 8 - much worse	0 participants	1 participants	2 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 8 - very much worse	1 participants	1 participants	0 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 12 - very much improved	11 participants	3 participants	4 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 12 - much improved	16 participants	10 participants	12 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 12 - minimally improved	22 participants	24 participants	24 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 12 - no change	15 participants	36 participants	40 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 16 - minimally worse	2 participants	2 participants	5 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 16 - much worse	1 participants	0 participants	0 participants
Patient Global Impression of Change (PGIC) - Full Analysis Set week 16 - very much worse	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: At weeks 4, 8, 12 and 16

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Patient Global Impression of Change (PGIC) - Per Protocol Set week 16 - very much worse	0 participants	0 participants	0 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 4 - Very Much Improved	10 participants	2 participants	4 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 4 - Much Improved	18 participants	12 participants	18 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 4 - Minimally improved	17 participants	19 participants	20 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 4 - no change	20 participants	34 participants	36 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 4 - minimally worse	6 participants	4 participants	2 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 4 - much worse	1 participants	0 participants	0 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 4 - very much worse	0 participants	0 participants	0 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 8 - Very much improved	9 participants	3 participants	1 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 8 - much improved	21 participants	9 participants	15 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 8 - minimally improved	18 participants	21 participants	17 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 8 - no change	20 participants	34 participants	43 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 8 - minimally worse	1 participants	3 participants	2 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 8 - much worse	0 participants	1 participants	2 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 8 - very much worse	0 participants	0 participants	0 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 12 - very much improved	11 participants	3 participants	4 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 12 - much improved	13 participants	9 participants	11 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 12 - minimally improved	21 participants	23 participants	23 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 12 - no change	15 participants	33 participants	38 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 12 - minimally worse	5 participants	1 participants	0 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 12 - much worse	2 participants	1 participants	2 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 12 - very much worse	1 participants	0 participants	0 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 16 - very much improved	7 participants	3 participants	6 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 16 - much improved	22 participants	18 participants	15 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 16 - minimally improved	19 participants	17 participants	18 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 16 - no change	19 participants	30 participants	34 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 16 - minimally worse	2 participants	2 participants	5 participants
Patient Global Impression of Change (PGIC) - Per Protocol Set week 16 - much worse	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: At weeks 4, 8, 12 and 16

Population: Full analysis set (FAS): The FAS consisted of all patients randomized who took at least 1 dose of IMP and who had at least 1 postbaseline efficacy measurement for the primary endpoint.

EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up.

The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case).

Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.

• The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent.

Both for total and partial scores, the higher the score, the worse is the outcome.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=81 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=82 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=84 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set week 4	1.2 score on a scale Standard Deviation 9.91	3.8 score on a scale Standard Deviation 10.28	2.8 score on a scale Standard Deviation 8.86
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set week 8	2.7 score on a scale Standard Deviation 10.41	2.4 score on a scale Standard Deviation 8.92	2.1 score on a scale Standard Deviation 8.86
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set week 12	3.0 score on a scale Standard Deviation 10.10	3.0 score on a scale Standard Deviation 7.8	3.0 score on a scale Standard Deviation 8.59
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Full Analysis Set week 16	3.0 score on a scale Standard Deviation 13.04	4.8 score on a scale Standard Deviation 11.92	2.0 score on a scale Standard Deviation 11.71

SECONDARY outcome

Timeframe: Aat baseline and weeks 4, 8, 12 and 16

Population: Per protocol (PP) set: The PP set consisted of all patients in the FAS who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and had no major deviations that may have affected study results.

EQ-5D is a standardised measure of health status. - The EQ-5D 3 level version (EQ-5D-3L) consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) which are summed up.

The EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. This scale ranges from 5 (best case) to 15 (worst case).

Each dimension has 3 levels: no problems, some problems, extreme problems (labelled 1-3). The respondent must indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.

• The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This is a quantitative measure of health outcome, judged by each respondent.

Both for total and partial scores, the higher the score, the worse is the outcome.

Outcome measures

Measure	rhNGF 20 μg/ml TID n=72 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD n=71 Participants One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID n=80 Participants Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set week 4	1.2 score on a scale Standard Deviation 9.98	3.6 score on a scale Standard Deviation 8.12	2.8 score on a scale Standard Deviation 8.99
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set week 8	2.7 score on a scale Standard Deviation 10.67	2.3 score on a scale Standard Deviation 9.02	2.2 score on a scale Standard Deviation 8.79
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set week 12	3.6 score on a scale Standard Deviation 9.77	3.4 score on a scale Standard Deviation 5.00	3.0 score on a scale Standard Deviation 8.71
Change From Baseline in EQ-5D-3L Questionnaire to Different Timepoints - Per Protocol Set week 16	3.3 score on a scale Standard Deviation 13.24	4.7 score on a scale Standard Deviation 8.84	1.9 score on a scale Standard Deviation 11.90

Adverse Events

rhNGF 20 μg/ml TID - Treatment Period

Serious events: 0 serious events

Other events: 65 other events

Deaths: 0 deaths

rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period

Serious events: 0 serious events

Other events: 60 other events

Deaths: 0 deaths

Vehicle TID - Treatment Period

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

rhNGF 20 μg/ml TID - Follow-up Period

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Vehicle TID - Follow up Period

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	rhNGF 20 μg/ml TID - Treatment Period n=85 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period n=84 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID - Treatment Period n=88 participants at risk Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml TID - Follow-up Period n=85 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period n=84 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID - Follow up Period n=88 participants at risk Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Cardiac disorders Atrial fibrillation	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).

Other adverse events

Measure	rhNGF 20 μg/ml TID - Treatment Period n=85 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD - Treatment Period n=84 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID - Treatment Period n=88 participants at risk Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml TID - Follow-up Period n=85 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours) rhNGF 20 μg/ml: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)	rhNGF 20 μg/ml BID + Vehicle OD - Follow-up Period n=84 participants at risk One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours) rhNGF 20 μg/ml + vehicle: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours). rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.	Vehicle TID - Follow up Period n=88 participants at risk Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours) Vehicle: one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Ear and labyrinth disorders Ear pain	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Asthenopia	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Blepharitis	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Blepharospasm	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Chalazion	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Conjunctival Disorder	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Conjunctival Haemorrhage	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Conjunctival Hyperaemia	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Diplopia	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Dry Eye	1.2% 1/85 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	3.6% 3/84 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	5.7% 5/88 • Number of events 6 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/85 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Erythema Of Eyelid	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eye Allergy	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eye Discharge	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eye Disorder	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eye Irritation	2.4% 2/85 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	6.0% 5/84 • Number of events 14 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	5.7% 5/88 • Number of events 6 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 5 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	4.5% 4/88 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eye Pain	63.5% 54/85 • Number of events 68 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	50.0% 42/84 • Number of events 73 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	4.5% 4/88 • Number of events 5 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eye Pruritus	2.4% 2/85 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/85 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eye Swelling	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eyelid Disorder	1.2% 1/85 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	3.6% 3/84 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eyelid Irritation	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eyelid Oedema	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Eyelid Pain	3.5% 3/85 • Number of events 6 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	10.7% 9/84 • Number of events 15 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Foreign Body Sensation In Eyes	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	3.6% 3/84 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Lacrimation Increased	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Meibomian Gland Dysfunction	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Ocular Discomfort	7.1% 6/85 • Number of events 9 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	4.8% 4/84 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Ocular Hyperaemia	2.4% 2/85 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	3.6% 3/84 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	3.4% 3/88 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/85 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Photophobia	7.1% 6/85 • Number of events 6 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	4.8% 4/84 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Posterior Capsule Opacification	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Refraction Disorder	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Swelling Of Eyelid	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	7.1% 6/84 • Number of events 6 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Vision Blurred	3.5% 3/85 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.3% 2/88 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Visual Acuity Reduced	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Visual Impairment	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Eye disorders Vitreous Floaters	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Gastrointestinal disorders Constipation	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Gastrointestinal disorders Inguinal Hernia	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Gastrointestinal disorders Nausea	3.5% 3/85 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
General disorders Instillation Site Irritation	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
General disorders Instillation Site Pain	2.4% 2/85 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Bronchitis	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Hordeolum	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Influenza	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Kidney Infection	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Nasopharyngitis	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.3% 2/88 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Sinusitis	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	3.4% 3/88 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Upper Respiratory Tract	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	3.5% 3/85 • Number of events 3 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Urinary Tract Infection	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Infections and infestations Viral Infection	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Injury, poisoning and procedural complications Back Injury	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Injury, poisoning and procedural complications Ligament Sprain	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Injury, poisoning and procedural complications Superficial Injury Of Eye	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Musculoskeletal and connective tissue disorders Arthritis	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	2.4% 2/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Nervous system disorders Dizziness	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Nervous system disorders Headache	9.4% 8/85 • Number of events 9 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	6.0% 5/84 • Number of events 5 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	4.5% 4/88 • Number of events 4 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Nervous system disorders Hypoaesthesia	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Nervous system disorders Migraine	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Nervous system disorders Migraine With Aura	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 2 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Renal and urinary disorders Bladder Prolapse	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Respiratory, thoracic and mediastinal disorders Dysphonia	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Respiratory, thoracic and mediastinal disorders Sinus Congestion	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Respiratory, thoracic and mediastinal disorders Throat Irritation	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.1% 1/88 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Skin and subcutaneous tissue disorders Rash	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/84 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Vascular disorders Hot Flush	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).
Vascular disorders Lymphoedema	0.00% 0/85 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	1.2% 1/85 • Number of events 1 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/84 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).	0.00% 0/88 • From Screening day to week 16 More specifically, adverse events are assessed at Screening day, Visit 1 Day 1), Visit 2 (Day 14), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84), Visit 6 (Day 112).

Additional Information

Clinical Development & Operations

Dompé farmaceutici s.p.a.

Phone: +39 02 583831

Email: clinical.trials@dompe.com

Results disclosure agreements

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