Trial Outcomes & Findings for Efficacy and Safety of Dexamethasone Nanoparticles Eye Drops in Diabetic Macular Edema (NCT NCT05343156)

Last Updated: 2022-06-28

Results Overview

The primary efficacy endpoint was summarized by treatment group using descriptive statistics, including 70%, 90% and 95% confidence intervals (CIs). Change from baseline to Week 12 is also summarised by treatment group. The primary analysis of the primary endpoint employed a linear model with change from baseline ETDRS BCVA letters as the response, baseline ETDRS BCVA letters as a covariate, and treatment as a main effect factor, using the ITT population and with multiple imputation pattern mixture model techniques used to impute missing data.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

144 participants

Primary outcome timeframe

Baseline & Week 12

Results posted on

2022-06-28

Participant Flow

Participant milestones

Participant milestones
Measure	DexNP Eye Drop The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	Vehicle Eye Drop The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Overall Study STARTED	99	45
Overall Study COMPLETED	91	42
Overall Study NOT COMPLETED	8	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of Dexamethasone Nanoparticles Eye Drops in Diabetic Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DexNP Eye Drop n=99 Participants The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	Vehicle Eye Drop n=45 Participants The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	Total n=144 Participants Total of all reporting groups
Age, Continuous	63.6 years STANDARD_DEVIATION 9.5 • n=5 Participants	66.1 years STANDARD_DEVIATION 9.92 • n=7 Participants	64.4 years STANDARD_DEVIATION 9.67 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	17 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	28 Participants n=7 Participants	92 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	98 Participants n=5 Participants	45 Participants n=7 Participants	143 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline & Week 12

Population: Change from baseline to week 12 in Study Eye ETDRS BCVA Letters using Multiple Imputation (Intent-to-Treat Population)

Outcome measures

Outcome measures
Measure	DexNP Eye Drop n=99 Participants The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	Vehicle Eye Drop n=45 Participants The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Mean Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA)	2.62 ETDRS BCVA Letters Interval 1.831 to 3.403	1.04 ETDRS BCVA Letters Interval -0.115 to 2.189

Adverse Events

DexNP Eye Drop

Serious events: 11 serious events

Other events: 32 other events

Deaths: 2 deaths

Vehicle Eye Drop

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DexNP Eye Drop n=99 participants at risk The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	Vehicle Eye Drop n=45 participants at risk The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Cardiac disorders Atrial fibrillation	2.0% 2/99 • Number of events 2 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Cardiac disorders Cardiac failure	2.0% 2/99 • Number of events 2 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Cardiac disorders Myocardial infarction	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Endocrine disorders Type 2 diabetes mellitus	1.0% 1/99 • Number of events 2 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
General disorders Death	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
General disorders Sudden cardiac death	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders Retinal detachment	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Endocrine disorders diabetic ulcer	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Infections and infestations Influenza	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Infections and infestations Urinary tract infection	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Vascular disorders Peripheral arterial occlusive disease	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)

Other adverse events

Additional Information

Bastian Dehmel, Chief Development Officer

Oculis SA

Phone: 0041 21 711 39 70

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator agrees not to publish/present the results until such time as the aggregate study results are published. After such time, Investigator may publish the results in accordance with the following: Investigator shall submit to Sponsor any such proposed publication/presentation resulting from or relating to the Study at least 60 days prior to the submission for publication. Sponsor may require the delay of publication/presentation for an additional period of time not to exceed 120 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	DexNP Eye Drop n=99 participants at risk The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	Vehicle Eye Drop n=45 participants at risk The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Investigations Intraocular pressure increased	21.2% 21/99 • Number of events 23 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Investigations Blood glucose fluctuation	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders Eye irritation	3.0% 3/99 • Number of events 3 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders Ocular hypertension	3.0% 3/99 • Number of events 3 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders Cataract subcapscular	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders conjunctival hemorrhage	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders Diabetic retinal edema	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders erythema of eyelid	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders eyelid ptosis	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders glaucoma	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders noninfective conjunctivitis	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders Ocular hyperemia	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders photophobia	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders posterior capsule opacification	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders conjunctival hyperemia	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders conjunctivitis	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders corneal edema	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders eye infection bacterial	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders eye pruritus	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders foreign body sensation in eyes	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders keratopathy	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Eye disorders retinal pigment epitheliopathy	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Nervous system disorders dysgeusia	2.0% 2/99 • Number of events 2 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Respiratory, thoracic and mediastinal disorders dyspnea	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Psychiatric disorders insomnia	1.0% 1/99 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	0.00% 0/45 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Infections and infestations conjunctivitis	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Infections and infestations eye infection bacterial	0.00% 0/99 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)	2.2% 1/45 • Number of events 1 • Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)