Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of a Fixed Combination Ocular Insert in Participants With Open-angle Glaucoma or Ocular Hypertension (NCT NCT02742649)

Last Updated: 2019-02-25

Results Overview

IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour). The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

55 participants

Primary outcome timeframe

Day 8

Results posted on

2019-02-25

Participant Flow

Participant milestones

Participant milestones
Measure	Washout + Placebo Ocular Insert During the washout period, participants wore a placebo insert in each eye serving as a trial-wear period for 24 to 48 days.	Fixed Combination (FC) Ocular Insert Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Timolol 0.5% Ophthalmic Drops Following a second washout period, timolol drops, 0.5% solution twice daily in each eye from Day 99 to 112.
Pre-Randomization Washout Period STARTED	55	0	0	0	0
Pre-Randomization Washout Period COMPLETED	50	0	0	0	0
Pre-Randomization Washout Period NOT COMPLETED	5	0	0	0	0
Double-Blind Treatment Period STARTED	0	17	17	16	0
Double-Blind Treatment Period COMPLETED	0	16	17	16	0
Double-Blind Treatment Period NOT COMPLETED	0	1	0	0	0
Open-Label Period STARTED	0	0	0	0	49
Open-Label Period COMPLETED	0	0	0	0	48
Open-Label Period NOT COMPLETED	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Washout + Placebo Ocular Insert During the washout period, participants wore a placebo insert in each eye serving as a trial-wear period for 24 to 48 days.	Fixed Combination (FC) Ocular Insert Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Timolol 0.5% Ophthalmic Drops Following a second washout period, timolol drops, 0.5% solution twice daily in each eye from Day 99 to 112.
Pre-Randomization Washout Period Washout/Randomization Failure	5	0	0
Double-Blind Treatment Period Adverse Event	0	1	0
Open-Label Period Lost to Follow-up	0	0	1

Baseline Characteristics

A Study to Evaluate Efficacy and Safety of a Fixed Combination Ocular Insert in Participants With Open-angle Glaucoma or Ocular Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fixed Combination (FC) Ocular Inset n=17 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	Total n=50 Participants Total of all reporting groups
Age, Continuous	67.24 years STANDARD_DEVIATION 12.94 • n=93 Participants	68.94 years STANDARD_DEVIATION 5.75 • n=4 Participants	67.56 years STANDARD_DEVIATION 9.27 • n=27 Participants	67.92 years STANDARD_DEVIATION 9.61 • n=483 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	11 Participants n=4 Participants	11 Participants n=27 Participants	36 Participants n=483 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	6 Participants n=4 Participants	5 Participants n=27 Participants	14 Participants n=483 Participants
Intraocular Pressure (IOP) Randomization (T=0 hour)	24.34 mm Hg STANDARD_DEVIATION 2.06 • n=93 Participants	24.30 mm Hg STANDARD_DEVIATION 1.89 • n=4 Participants	24.18 mm Hg STANDARD_DEVIATION 1.78 • n=27 Participants	24.27 mm Hg STANDARD_DEVIATION 1.88 • n=483 Participants
Intraocular Pressure (IOP) Randomization (T=4 hour)	22.98 mm Hg STANDARD_DEVIATION 2.92 • n=93 Participants	22.93 mm Hg STANDARD_DEVIATION 3.06 • n=4 Participants	23.33 mm Hg STANDARD_DEVIATION 2.77 • n=27 Participants	23.07 mm Hg STANDARD_DEVIATION 2.87 • n=483 Participants
Intraocular Pressure (IOP) Randomization (T=8 hour)	22.44 mm Hg STANDARD_DEVIATION 2.57 • n=93 Participants	22.90 mm Hg STANDARD_DEVIATION 3.13 • n=4 Participants	23.03 mm Hg STANDARD_DEVIATION 2.70 • n=27 Participants	22.78 mm Hg STANDARD_DEVIATION 2.77 • n=483 Participants

PRIMARY outcome

Timeframe: Day 8

Population: FAS included all participants who were randomized, treated and returned for at least one (1) regularly scheduled post-treatment visit. Participants were analyzed in the treatment group to which they were randomized (Double Blind Treatment Period).

Outcome measures

Outcome measures
Measure	Fixed Combination (FC) Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.
Intraocular Pressure (IOP) on Day 8 Day 8 (T=0 hour)	17.83 mm Hg Standard Deviation 3.39	19.15 mm Hg Standard Deviation 2.62	19.59 mm Hg Standard Deviation 4.68
Intraocular Pressure (IOP) on Day 8 Day 8 (T=4 hour)	17.51 mm Hg Standard Deviation 3.18	18.96 mm Hg Standard Deviation 4.14	19.88 mm Hg Standard Deviation 5.42
Intraocular Pressure (IOP) on Day 8 Day 8 (T=8 hour)	17.05 mm Hg Standard Deviation 3.32	17.84 mm Hg Standard Deviation 4.00	19.66 mm Hg Standard Deviation 4.54

PRIMARY outcome

Timeframe: Day 16

Outcome measures

Outcome measures
Measure	Fixed Combination (FC) Ocular Insert n=15 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.
IOP on Day 16 Day 16 (T=0 hour)	18.29 mm Hg Standard Deviation 3.86	18.08 mm Hg Standard Deviation 3.98	20.81 mm Hg Standard Deviation 5.22
IOP on Day 16 Day 16 (T=4 hour)	17.95 mm Hg Standard Deviation 3.10	18.64 mm Hg Standard Deviation 4.17	21.08 mm Hg Standard Deviation 5.46
IOP on Day 16 Day 16 (T=8 hour)	17.21 mm Hg Standard Deviation 4.14	18.54 mm Hg Standard Deviation 3.73	19.43 mm Hg Standard Deviation 3.77

PRIMARY outcome

Timeframe: Day 28

Outcome measures

Outcome measures
Measure	Fixed Combination (FC) Ocular Insert n=16 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.
IOP on Day 28 Day 28 (T=0 hour)	18.03 mm Hg Standard Deviation 4.21	18.44 mm Hg Standard Deviation 4.23	19.75 mm Hg Standard Deviation 4.80
IOP on Day 28 Day 28 (T=4 hour)	18.54 mm Hg Standard Deviation 3.50	19.59 mm Hg Standard Deviation 3.70	20.09 mm Hg Standard Deviation 4.67
IOP on Day 28 Day 28 (T=8 hour)	17.26 mm Hg Standard Deviation 2.60	18.77 mm Hg Standard Deviation 4.13	19.20 mm Hg Standard Deviation 3.60

PRIMARY outcome

Timeframe: Day 49

Outcome measures

Outcome measures
Measure	Fixed Combination (FC) Ocular Insert n=15 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.
IOP on Day 49 Day 49 (T=0 hour)	18.55 mm Hg Standard Deviation 4.05	18.88 mm Hg Standard Deviation 4.52	18.63 mm Hg Standard Deviation 3.89
IOP on Day 49 Day 49 (T=4 hour)	17.77 mm Hg Standard Deviation 4.02	19.35 mm Hg Standard Deviation 3.51	19.67 mm Hg Standard Deviation 3.54
IOP on Day 49 Day 49 (T=8 hour)	17.23 mm Hg Standard Deviation 4.53	18.48 mm Hg Standard Deviation 3.57	19.13 mm Hg Standard Deviation 2.40

PRIMARY outcome

Timeframe: Day 70

Outcome measures

Outcome measures
Measure	Fixed Combination (FC) Ocular Insert n=16 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.
IOP on Day 70 Day 70 (T=0 hour)	17.60 mm Hg Standard Deviation 2.94	17.78 mm Hg Standard Deviation 2.58	17.79 mm Hg Standard Deviation 4.36
IOP on Day 70 Day 70 (T=4 hour)	18.09 mm Hg Standard Deviation 3.73	18.71 mm Hg Standard Deviation 3.59	18.48 mm Hg Standard Deviation 4.23
IOP on Day 70 Day 70 (T=8 hour)	17.14 mm Hg Standard Deviation 2.64	18.61 mm Hg Standard Deviation 4.07	18.78 mm Hg Standard Deviation 4.13

SECONDARY outcome

Timeframe: From Randomization (Day 0) to Day 70

Population: Safety population set included all randomized participants who had an ocular insert placed at the Randomization Visit. In this analysis set, participants were analyzed according to the treatment received during each study treatment period.

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with adverse events related to the eye as well as number of participants with all other adverse events.

Outcome measures

Outcome measures
Measure	Fixed Combination (FC) Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.
Number of Participants With Ocular and Non-Ocular Adverse Events Ocular	13 Participants	14 Participants	10 Participants
Number of Participants With Ocular and Non-Ocular Adverse Events Non-Ocular	11 Participants	10 Participants	5 Participants

SECONDARY outcome

Timeframe: Day 98, Day 112

IOP is a measurement of the fluid pressure inside the eye. IOP was measured at the following three time points: 8 am (T=0 hour), 12 pm (T=4 hour) and 4 pm (T=8 hour) at the start (Day 98) and end (Day 112) of the Open Label Period during which participants were treated with timolol 0.5% ophthalmic solution twice daily. The IOP measured in the two eyes was averaged to compute a single IOP value for each timepoint.

Outcome measures

Outcome measures
Measure	Fixed Combination (FC) Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.	Bimatoprost Ocular Insert n=17 Participants Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98.	Timolol Ocular Insert n=16 Participants Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98.
IOP During Open Label Period Day 98 (T=0 hour)	22.61 mm Hg Standard Deviation 2.41	22.69 mm Hg Standard Deviation 3.06	23.24 mm Hg Standard Deviation 3.54
IOP During Open Label Period Day 98 (T=4 hour)	21.67 mm Hg Standard Deviation 2.42	22.38 mm Hg Standard Deviation 3.16	22.99 mm Hg Standard Deviation 4.25
IOP During Open Label Period Day 98 (T=8 hour)	20.74 mm Hg Standard Deviation 1.65	22.88 mm Hg Standard Deviation 3.89	22.63 mm Hg Standard Deviation 3.92
IOP During Open Label Period Day 112 (T=0 hour)	19.21 mm Hg Standard Deviation 3.59	20.65 mm Hg Standard Deviation 3.90	19.71 mm Hg Standard Deviation 1.59
IOP During Open Label Period Day 112 (T=4 hour)	17.62 mm Hg Standard Deviation 3.41	18.52 mm Hg Standard Deviation 3.97	18.75 mm Hg Standard Deviation 4.26
IOP During Open Label Period Day 112 (T=8 hour)	17.51 mm Hg Standard Deviation 3.98	18.43 mm Hg Standard Deviation 4.45	18.19 mm Hg Standard Deviation 3.69

Adverse Events

Fixed Combination (FC) Ocular Inset

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Bimatoprost Ocular Insert

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Timolol Ocular Insert

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Fixed Combination (FC) Ocular Inset n=17 participants at risk Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	Bimatoprost Ocular Insert n=17 participants at risk Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	Timolol Ocular Insert n=16 participants at risk Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.
Cardiac disorders Mitral valve incompetence	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Surgical and medical procedures Knee arthroplasty	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)

Other adverse events

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No presentation or publication of Institution's data relating to the Trial may occur until after the Trial has been completed at all sites. If Investigator desires to present or publish, investigator must submit any and all manuscripts, posters, abstracts, or other intended publications (hereinafter collectively referred to as "manuscripts") to Sponsor at least sixty (60) days prior to the actual submission of such manuscript(s) for publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Fixed Combination (FC) Ocular Inset n=17 participants at risk Following washout period, one segment of bimatoprost and one segment of timolol maleate were combined in an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	Bimatoprost Ocular Insert n=17 participants at risk Following washout period, one segment of bimatoprost and one placebo segment were combined in an ocular ring and inserted in each eye for 70 days followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.	Timolol Ocular Insert n=16 participants at risk Following washout period, one segment of timolol and one placebo segment were combined into an ocular ring and inserted in each eye for 70 days, followed by a second washout period from Day 71 to 98. Following the second washout period, 0.5% timolol drops twice daily in each eye from Day 99 to 112.
Eye disorders Eye discharge	29.4% 5/17 • Randomization (Day 0) to the end of the study (Day 112)	29.4% 5/17 • Randomization (Day 0) to the end of the study (Day 112)	31.2% 5/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Conjunctival disorder	23.5% 4/17 • Randomization (Day 0) to the end of the study (Day 112)	11.8% 2/17 • Randomization (Day 0) to the end of the study (Day 112)	31.2% 5/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Eye irritation	29.4% 5/17 • Randomization (Day 0) to the end of the study (Day 112)	23.5% 4/17 • Randomization (Day 0) to the end of the study (Day 112)	12.5% 2/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Conjunctival hyperaemia	29.4% 5/17 • Randomization (Day 0) to the end of the study (Day 112)	11.8% 2/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Ocular discomfort	23.5% 4/17 • Randomization (Day 0) to the end of the study (Day 112)	17.6% 3/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Conjunctivitis	17.6% 3/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	12.5% 2/16 • Randomization (Day 0) to the end of the study (Day 112)
Skin and subcutaneous tissue disorders Pruritus	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	23.5% 4/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Punctate Keratitis	17.6% 3/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Vision Blurred	11.8% 2/17 • Randomization (Day 0) to the end of the study (Day 112)	11.8% 2/17 • Randomization (Day 0) to the end of the study (Day 112)	12.5% 2/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Eyelid Oedema	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	11.8% 2/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Infections and infestations Upper respiratory tract infection	41.2% 7/17 • Randomization (Day 0) to the end of the study (Day 112)	41.2% 7/17 • Randomization (Day 0) to the end of the study (Day 112)	12.5% 2/16 • Randomization (Day 0) to the end of the study (Day 112)
Nervous system disorders Headache	17.6% 3/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	12.5% 2/16 • Randomization (Day 0) to the end of the study (Day 112)
Musculoskeletal and connective tissue disorders Back pain	11.8% 2/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Keratitis	11.8% 2/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Foreign body sensation in eyes	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Lacrimation increased	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Dry eye	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Erythema of eyelid	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Lagophthalmos	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Photophobia	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Eye disorders Retinal artery occlusion	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Gastrointestinal disorders Diarrhoea	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Gastrointestinal disorders Gastritis	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Hepatobiliary disorders Hepatic steatosis	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Infections and infestations Conjunctivitis viral	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Infections and infestations Urinary tract infection	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)
Infections and infestations Erysipelas	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Infections and infestations Infected skin ulcer	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Injury, poisoning and procedural complications Ligament sprain	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Nervous system disorders Dizziness	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	5.9% 1/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/16 • Randomization (Day 0) to the end of the study (Day 112)
Ear and labyrinth disorders Vertigo	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	0.00% 0/17 • Randomization (Day 0) to the end of the study (Day 112)	6.2% 1/16 • Randomization (Day 0) to the end of the study (Day 112)