Trial Outcomes & Findings for Suprachoroidal Injection of Triamcinolone Acetonide With IVT Aflibercept in Subjects With Macular Edema Following RVO (NCT NCT02980874)

Last Updated: 2021-04-14

Results Overview

Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

460 participants

Primary outcome timeframe

2 months

Results posted on

2021-04-14

Participant Flow

Participant milestones

Participant milestones
Measure	Active IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept
Overall Study STARTED	231	229
Overall Study COMPLETED	128	127
Overall Study NOT COMPLETED	103	102

Reasons for withdrawal

Reasons for withdrawal
Measure	Active IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept
Overall Study Adverse Event	2	7
Overall Study Withdrawal by Subject	7	2
Overall Study Lost to Follow-up	5	5
Overall Study Includes premature discontinuation due to study termination.	88	88
Overall Study Unknown study completion status	1	0

Baseline Characteristics

Suprachoroidal Injection of Triamcinolone Acetonide With IVT Aflibercept in Subjects With Macular Edema Following RVO

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active n=231 Participants IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control n=229 Participants IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept	Total n=460 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	89 Participants n=5 Participants	107 Participants n=7 Participants	196 Participants n=5 Participants
Age, Categorical >=65 years	142 Participants n=5 Participants	122 Participants n=7 Participants	264 Participants n=5 Participants
Age, Continuous	66.4 Years STANDARD_DEVIATION 12.31 • n=5 Participants	64.9 Years STANDARD_DEVIATION 12.42 • n=7 Participants	65.7 Years STANDARD_DEVIATION 12.37 • n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	105 Participants n=7 Participants	202 Participants n=5 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	124 Participants n=7 Participants	258 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	33 Participants n=5 Participants	40 Participants n=7 Participants	73 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	181 Participants n=5 Participants	177 Participants n=7 Participants	358 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Hungary	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	182 Participants n=5 Participants	183 Participants n=7 Participants	365 Participants n=5 Participants
Region of Enrollment Philippines	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United Kingdom	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Portugal	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment India	13 Participants n=5 Participants	19 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment Spain	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Canada	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Taiwan	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Denmark	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Poland	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Slovakia	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Australia	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Type of Retinal Vein Occlusion Branch retinal vein occlusion	124 Participants n=5 Participants	124 Participants n=7 Participants	248 Participants n=5 Participants
Type of Retinal Vein Occlusion Central retinal vein occlusion	107 Participants n=5 Participants	105 Participants n=7 Participants	212 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 months

Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment.

Outcome measures

Outcome measures
Measure	Active n=231 Participants IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control n=229 Participants IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept
Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS)	114 Participants	127 Participants

SECONDARY outcome

Timeframe: 6 months

Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment.

Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision.

Outcome measures

Outcome measures
Measure	Active n=231 Participants IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control n=229 Participants IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept
Mean Change From Baseline in Best Corrected Visual Acuity	15.5 Letters Standard Error 0.85	20.5 Letters Standard Error 0.85

SECONDARY outcome

Timeframe: 6 months

Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment.

Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.

Outcome measures

Outcome measures
Measure	Active n=231 Participants IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control n=210 Participants IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept
Mean Change From Baseline in Central Subfield Thickness	-354.3 Microns Standard Error 8.01	-416.2 Microns Standard Error 8.05

Adverse Events

Active

Serious events: 25 serious events

Other events: 128 other events

Deaths: 0 deaths

Control

Serious events: 28 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Active n=231 participants at risk IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control n=229 participants at risk IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept
Eye disorders Cataract	9.1% 21/231 • Number of events 29 • Adverse events were collected over 48 weeks of follow-up.	3.9% 9/229 • Number of events 12 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Cataract subcapsular	8.7% 20/231 • Number of events 22 • Adverse events were collected over 48 weeks of follow-up.	1.3% 3/229 • Number of events 3 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Conjunctival haemorrhage	18.2% 42/231 • Number of events 65 • Adverse events were collected over 48 weeks of follow-up.	12.2% 28/229 • Number of events 31 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Eye pain	8.7% 20/231 • Number of events 24 • Adverse events were collected over 48 weeks of follow-up.	4.8% 11/229 • Number of events 11 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Macular oedema	3.5% 8/231 • Number of events 11 • Adverse events were collected over 48 weeks of follow-up.	5.7% 13/229 • Number of events 16 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Visual acuity reduced	6.9% 16/231 • Number of events 18 • Adverse events were collected over 48 weeks of follow-up.	2.6% 6/229 • Number of events 7 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Vitreous detachment	5.6% 13/231 • Number of events 16 • Adverse events were collected over 48 weeks of follow-up.	3.9% 9/229 • Number of events 10 • Adverse events were collected over 48 weeks of follow-up.
Investigations Intraocular pressure increased	14.3% 33/231 • Number of events 51 • Adverse events were collected over 48 weeks of follow-up.	3.9% 9/229 • Number of events 13 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Nasopharyngitis	3.9% 9/231 • Number of events 9 • Adverse events were collected over 48 weeks of follow-up.	5.7% 13/229 • Number of events 13 • Adverse events were collected over 48 weeks of follow-up.
Vascular disorders Hypertension	6.5% 15/231 • Number of events 18 • Adverse events were collected over 48 weeks of follow-up.	6.6% 15/229 • Number of events 17 • Adverse events were collected over 48 weeks of follow-up.

Additional Information

Thomas Ciulla, MD MBA

Clearside Biomedical, Inc.

Phone: (678) 392-2318

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The institutions and Investigators participating in this study shall have no right to publish or present the results of this study without the prior written consent of Clearside Biomedical, Inc.
Publication restrictions are in place

Restriction type: OTHER

Measure	Active n=231 participants at risk IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA IVT aflibercept: 2 mg intravitreal injection of aflibercept	Control n=229 participants at risk IVT aflibercept (2 mg/0.05 mL) + sham SC procedure suprachoroidal sham: suprachoroidal sham procedure IVT aflibercept: 2 mg intravitreal injection of aflibercept
Blood and lymphatic system disorders Anaemia	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	1.3% 3/229 • Number of events 3 • Adverse events were collected over 48 weeks of follow-up.
Cardiac disorders Acute coronary syndrome	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Cardiac disorders Atrial fibrillation	0.87% 2/231 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Cardiac disorders Coronary artery disease	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.87% 2/229 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.
Cardiac disorders Myocardial infarction	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.87% 2/229 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Cataract	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Retinal detachment	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Ulcerative keratitis	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Visual acuity reduced	0.87% 2/231 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Eye disorders Vitreous haemorrhage	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Gastrointestinal disorders Gastritis	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Gastrointestinal disorders Pancreatitis acute	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
General disorders Abasia	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
General disorders Chest pain	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.87% 2/229 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.
General disorders Pyrexia	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Appendicitis perforated	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Bronchitis	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Colonic abscess	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Diverticulitis	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Empyema	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Endophthalmitis	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Hepatitis C	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Perirectal abscess	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Pneumonia	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Pyelonephritis	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Infections and infestations Urinary tract infection	0.87% 2/231 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Alcohol poisoning	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Fall	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Head injury	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Multiple fractures	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Pelvic fracture	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Rib fracture	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Road traffic accident	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Spinal fracture	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Injury, poisoning and procedural complications Sternal fracture	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Investigations Intraocular pressure increased	1.3% 3/231 • Number of events 3 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Metabolism and nutrition disorders Dehydration	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Metabolism and nutrition disorders Hyponatraemia	0.87% 2/231 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Metabolism and nutrition disorders Lactic acidosis	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Musculoskeletal and connective tissue disorders Rotor cuff syndrome	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer metastatic	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Paraganglion neoplasm malignant	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Balance disorder	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Cerebrovascular accident	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Coma	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Dizziness	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Facial paralysis	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Hemiplegia	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Syncope	0.87% 2/231 • Number of events 2 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Transient global amnesia	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Nervous system disorders Transient ischaemic attack	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	1.3% 3/229 • Number of events 3 • Adverse events were collected over 48 weeks of follow-up.
Psychiatric disorders Major depression	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Psychiatric disorders Mental status changes	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Renal and urinary disorders Acute kidney injury	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Renal and urinary disorders Haematuria	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Reproductive system and breast disorders Pelvic pain	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Reproductive system and breast disorders Prostatomegaly	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Vascular disorders Aortic arteriosclerosis	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.
Vascular disorders Aortic stenosis	0.00% 0/231 • Adverse events were collected over 48 weeks of follow-up.	0.44% 1/229 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.
Vascular disorders Hypertension	0.43% 1/231 • Number of events 1 • Adverse events were collected over 48 weeks of follow-up.	0.00% 0/229 • Adverse events were collected over 48 weeks of follow-up.