Trial Outcomes & Findings for ESBA1008 Safety, Tolerability and Effects in Wet Age-Related Macular Degeneration (AMD) Patients (NCT NCT01304693)

NCT ID: NCT01304693

Last Updated: 2014-07-17

Results Overview

CSFT is a retinal thickness measurement and was measured with SD-OCT. A thickening of the retina is characteristic of wet AMD, and a reduction in CSFT may indicate an improvement in ocular health. One eye (ie, study eye) contributed to the mean.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 376 participants
• Primary outcome timeframe: Baseline, Month 1
• Results posted on: 2014-07-17

Participant Flow

Subjects were recruited from 51 investigational centers located in the United States, Europe, Israel, and Australia.

Of the 376 enrolled, 182 were exited as screen failures prior to exposure to randomization and exposure to the study drug. This reporting group includes all patients who were randomized, received study drug, and completed at least 1 scheduled on-therapy study visit (ITT) (194).

Participant milestones

Measure	ESBA1008 Dose A Single intravitreal injection with 6-month follow-up	ESBA1008 Dose B Single intravitreal injection with 6-month follow-up	ESBA1008 Dose C Single intravitreal injection with 6-month follow-up	ESBA1008 Dose D Single intravitreal injection with 6-month follow-up	Lucentis Single intravitreal injection with 6-month follow-up
Overall Study STARTED	10	35	48	40	61
Overall Study COMPLETED	10	35	47	39	60
Overall Study NOT COMPLETED	0	0	1	1	1

Reasons for withdrawal

Measure	ESBA1008 Dose A Single intravitreal injection with 6-month follow-up	ESBA1008 Dose B Single intravitreal injection with 6-month follow-up	ESBA1008 Dose C Single intravitreal injection with 6-month follow-up	ESBA1008 Dose D Single intravitreal injection with 6-month follow-up	Lucentis Single intravitreal injection with 6-month follow-up
Overall Study Adverse Event	0	0	0	0	1
Overall Study Decision Unrelated to an Adverse Event	0	0	1	1	0

Baseline Characteristics

ESBA1008 Safety, Tolerability and Effects in Wet Age-Related Macular Degeneration (AMD) Patients

Baseline characteristics by cohort

Measure	ESBA1008 Dose A n=10 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose B n=35 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose C n=48 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose D n=40 Participants Single intravitreal injection with 6-month follow-up	Lucentis n=61 Participants Single intravitreal injection with 6-month follow-up	Total n=194 Participants Total of all reporting groups
Age, Continuous	75.9 years STANDARD_DEVIATION 6.9 • n=5 Participants	78.5 years STANDARD_DEVIATION 8.3 • n=7 Participants	75.2 years STANDARD_DEVIATION 7.7 • n=5 Participants	74.5 years STANDARD_DEVIATION 9.8 • n=4 Participants	77.8 years STANDARD_DEVIATION 8.1 • n=21 Participants	76.5 years STANDARD_DEVIATION 8.4 • n=10 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants	25 Participants n=4 Participants	33 Participants n=21 Participants	106 Participants n=10 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	20 Participants n=7 Participants	21 Participants n=5 Participants	15 Participants n=4 Participants	28 Participants n=21 Participants	88 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline, Month 1

Population: This analysis population includes all patients who were randomized, received study drug, and completed at least 1 scheduled on-therapy study visit (ITT). Efficacy data from visits occurring after standard of care (SoC) were censored and replaced based on LOCF,i.e. by the data observed at the time of the SoC decision.

CSFT is a retinal thickness measurement and was measured with SD-OCT. A thickening of the retina is characteristic of wet AMD, and a reduction in CSFT may indicate an improvement in ocular health. One eye (ie, study eye) contributed to the mean.

Outcome measures

Measure	ESBA1008 Dose A n=10 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose B n=35 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose C n=48 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose D n=40 Participants Single intravitreal injection with 6-month follow-up	Lucentis n=61 Participants Single intravitreal injection with 6-month follow-up
Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT)	-142.3 microns Standard Deviation 78.8	-181.6 microns Standard Deviation 107.2	-175.6 microns Standard Deviation 138.9	-174.9 microns Standard Deviation 101.3	-159.4 microns Standard Deviation 110.1

SECONDARY outcome

Timeframe: Time to event, up to Month 6

Population: ITT: All patients who were randomized, received study drug, and completed at least 1 scheduled on-therapy study visit.

Standard of care (SOC) therapy for exudative AMD was implemented if any protocol-specified criteria relating to CSFT, best-corrected visual acuity, or clinically significant intraocular hemorrhages in the study eye were met, in the opinion of the Investigator.

Outcome measures

Measure	ESBA1008 Dose A n=10 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose B n=35 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose C n=48 Participants Single intravitreal injection with 6-month follow-up	ESBA1008 Dose D n=40 Participants Single intravitreal injection with 6-month follow-up	Lucentis n=61 Participants Single intravitreal injection with 6-month follow-up
Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria	45 Days Interval 30.0 to 60.0	75 Days Interval 45.0 to 120.0	67.5 Days Interval 37.5 to 120.0	75 Days Interval 37.5 to 150.0	45 Days Interval 25.0 to 75.0

Adverse Events

ESBA1008 Dose A

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

ESBA1008 Dose B

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

ESBA1008 Dose C

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

ESBA1008 Dose D

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Lucentis

Serious events: 7 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	ESBA1008 Dose A n=11 participants at risk Single intravitreal injection with 6-month follow-up	ESBA1008 Dose B n=31 participants at risk Single intravitreal injection with 6-month follow-up	ESBA1008 Dose C n=47 participants at risk Single intravitreal injection with 6-month follow-up	ESBA1008 Dose D n=44 participants at risk Single intravitreal injection with 6-month follow-up	Lucentis n=61 participants at risk Single intravitreal injection with 6-month follow-up
Nervous system disorders Cerebrovascular accident	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	1.6% 1/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Nervous system disorders Syncope	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Nervous system disorders Transient ischaemic attack	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Eye disorders Visual acuity reduced	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Skin and subcutaneous tissue disorders Blister	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.1% 1/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.1% 1/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Hepatobiliary disorders Hepatitis	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.1% 1/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Nervous system disorders Vertebrobasilar insufficiency	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.1% 1/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Cardiac disorders Acute myocardial infarction	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
General disorders Multi-organ failure	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Injury, poisoning and procedural complications Post-procedural haematoma	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Surgical and medical procedures Aortic bypass	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	1.6% 1/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Infections and infestations Cellulitis	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	1.6% 1/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	1.6% 1/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Infections and infestations Endophthalmitis	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	1.6% 1/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Infections and infestations Pneumonia	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.3% 2/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.

Other adverse events

Measure	ESBA1008 Dose A n=11 participants at risk Single intravitreal injection with 6-month follow-up	ESBA1008 Dose B n=31 participants at risk Single intravitreal injection with 6-month follow-up	ESBA1008 Dose C n=47 participants at risk Single intravitreal injection with 6-month follow-up	ESBA1008 Dose D n=44 participants at risk Single intravitreal injection with 6-month follow-up	Lucentis n=61 participants at risk Single intravitreal injection with 6-month follow-up
Eye disorders Conjunctival haemorrhage	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	9.7% 3/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	6.4% 3/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	18.2% 8/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.3% 2/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Infections and infestations Nasopharnygitis	9.1% 1/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	6.4% 3/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	6.8% 3/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.3% 2/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Eye disorders Retinal haemorrhage	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	4.3% 2/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	6.6% 4/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Eye disorders Visual acuity reduced	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	6.5% 2/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.1% 1/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	4.5% 2/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	4.9% 3/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Vascular disorders Hypertension	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	10.6% 5/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	4.5% 2/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Infections and infestations Urinary tract infection	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	12.9% 4/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.1% 1/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	4.5% 2/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Eye disorders Eye pain	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	8.5% 4/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	2.3% 1/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	1.6% 1/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Infections and infestations Bronchitis	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	6.4% 3/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	4.9% 3/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Infections and infestations Pneumonia	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	3.2% 1/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	4.9% 3/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/11 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/31 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	6.4% 3/47 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	0.00% 0/44 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.	1.6% 1/61 • Adverse events were collected for the duration of the study (2 years, 5 months). An AE was considered to be any untoward medical occurrence in a patient exposed to study drug. The AE did not have to have had a causal relationship with the study drug. This analysis population includes all patients exposed to the study drug, as treated. It should be noted that 6 patients were misdosed: 1 randomized to ESBA1008 B received ESBA1008 A; 1 randomized to ESBA1008 C received ESBA1008 B; and 4 randomized to ESBA1008 B received ESBA1008 D.

Additional Information

Georges Weissgerber, Executive Director, Novartis Pharma AG

Alcon Research, Ltd.

Phone: 1-888-451-3937

Email: alcon.medinfo@alcon.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
• Publication restrictions are in place

Restriction type: OTHER