Intravitreal LFG316 in Patients With Age-related Macular Degeneration (AMD)
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01527500
Collaborator
(none)
158
19
3
40.9
8.3
0.2
Study Details
Study Description
Brief Summary
This study was conducted in two parts; Part A and Part B: Part B was initially planned to include two cohorts. Cohort 2 was cancelled following an interim analysis for efficacy in Part A of the study, and not due to any safety issues or concerns. Cohort 2 is not referred to again and part B cohort 1 is referred to as part B alone in the remainder of the document and is the subject of this report.
Part B was conducted to assess the safety and tolerability of a single intravitreal (IVT) LFG316 10 mg/100 µL injection. There was no efficacy evaluation in Part B. The study employed a multicenter, randomized, sham - controlled, single masked design. Eight patients with advanced AMD were planned to be randomized in a 3:1 ratio to receive a single IVT dose of LFG316 (10 mg/100 µL) or sham injection. Patients assigned to a sham injection were treated the same as those assigned to LFG316, except that the hub of an empty syringe (without needle) was placed against the eye instead of the IVT injection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
158 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Sham-control, Proof-of-concept Study of Intravitreal LFG316 in Patients With Geographic Atrophy Associated With Age-related Macular Degeneration
Actual Study Start Date
:
Jan 25, 2012
Actual Primary Completion Date
:
Jun 24, 2015
Actual Study Completion Date
:
Jun 24, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LFG316 higher dose LFG316 10 mg/100 μL |
Drug: LFG316
LFG316 5 mg/50 μL solution for IVT injection,
|
| Sham Comparator: Sham Sham injection |
Drug: Sham
Sham injection (akin to intravitreal injection but without intravitreal needle; no investigational drug given)
|
| Experimental: LFG316 lower dose LFG316 5 mg/ 50 μL |
Drug: LFG316 Lower dose
LFG316 5 mg/50 μL solution for IVT Injection
|
Outcome Measures
Primary Outcome Measures
- Part A: Geographic Atrophy (GA) Lesion Growth Measured by Fundus Autofluorescence (FAF) From Baseline to Day 505 [Day 1 to Day 505 (starting from the day of first intravitreal injection until Day 505)]
Geographic atrophy (GA) lesion growth measured by fundus autofluorescence (FAF) from baseline to Day 505.
- Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence [The primary objective was from Day 1 to Day 337, however data was captured to Day 505 as exploratory objective]
Number is the Estimated Difference (95% CI) in lesion size.
- Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). [Day 1 to Day 85]
This primary outcome (for Part B) is reported under the Adverse Events section.
Secondary Outcome Measures
- Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence [Day 1 to Day 169 and Day 505 (starting from the day of first intravitreal injection until Day 505)]
Mean change in GA lesion growth from baseline to Day 169 and Day 505.
- Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham [Baseline Day 1, Day 169, Day 337 to Day 505]
Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: STUDY
- Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW [Baseline Day 1, Day 169, Day 337 to Day 505]
Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: FELLOW
- Part A: Concentrations of Total LFG316 in Blood During the Course of the Study [Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)]
Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=hours after the last administered dose e.g.; 0.0 means just before dosing. If the mean concentration is 0.00, that means there is no drug in the bloodstream
- Part A: Concentrations of Total C5 in Blood During the Course of the Study [Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559)]
Summary statistic of total C5 concentrations n=number of participants, h=scheduled sampling time
- Part B: AUC (Area Under the Curve) - Summary Statistics for PK Parameters [Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)]
Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=scheduled sampling time
- Tmax (hr) [Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)]
PART B: Tmax (Time of Maximum concentration observed) This is the highest concentration of drug in the blood that is measured after a dose. Cmax usually happens within a few hours after the dose is taken. The time that Cmax happens is referred to as Tmax. For some antiretroviral drugs, a high Cmax is thought to increase the risk of side effects from the drug.
- Part B: Cmax - Summary Statistic for PK Parameters [Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)]
Summary statistic for Part B of total LFG316 concentrations (pharmacokinetic analysis set) Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose
- Part B: Cmax_D - Summary Statistic for PK Parameters [Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85)]
Cmax_D=ng/mL/mg
Eligibility Criteria
Criteria
Ages Eligible for Study:
55 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of AMD if enrolled in Part B of study
-
Geographic atrophy in at least one eye if enrolled in Part A of study
-
ETDRS best corrected visual acuity of 60 letters or worse (~≤ 20/63)
Exclusion Criteria:
-
Retinal disease other than AMD
-
History of choroidal neovascularization
-
Severe cataract
-
History of infectious uveitis or endophthalmitis
-
Eye surgery in the non-study eye within 30 days prior to study
-
Eye surgery or IVT injection in the study eye within 90 days prior to study
-
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Phoenix | Arizona | United States | 85014 |
| 2 | Novartis Investigative Site | Phoenix | Arizona | United States | 85020 |
| 3 | Novartis Investigative Site | Tucson | Arizona | United States | 85704-5614 |
| 4 | Novartis Investigative Site | Beverly Hills | California | United States | 90211 |
| 5 | Novartis Investigative Site | Pasadena | California | United States | 91105-3153 |
| 6 | Novartis Investigative Site | Sacramento | California | United States | 95841 |
| 7 | Novartis Investigative Site | Colorado Springs | Colorado | United States | 80909 |
| 8 | Novartis Investigative Site | Fort Myers | Florida | United States | 33912-7125 |
| 9 | Novartis Investigative Site | Miami | Florida | United States | 33143 |
| 10 | Novartis Investigative Site | Winter Haven | Florida | United States | 33880 |
| 11 | Novartis Investigative Site | Atlanta | Georgia | United States | 30342 |
| 12 | Novartis Investigative Site | Leawood | Kansas | United States | 66211 |
| 13 | Novartis Investigative Site | Boston | Massachusetts | United States | 02114 |
| 14 | Novartis Investigative Site | Grand Rapids | Michigan | United States | 49546 |
| 15 | Novartis Investigative Site | Jackson | Michigan | United States | 49202 |
| 16 | Novartis Investigative Site | Charlotte | North Carolina | United States | 28210 |
| 17 | Novartis Investigative Site | Cincinnati | Ohio | United States | 45242 |
| 18 | Novartis Investigative Site | Cleveland | Ohio | United States | 44122 |
| 19 | Novartis Investigative Site | Silverdale | Washington | United States | 98383 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01527500
Other Study ID Numbers:
- CLFG316A2203
First Posted:
Feb 7, 2012
Last Update Posted:
Jan 5, 2021
Last Verified:
Mar 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study conducted in 2 parts: Part A & Part B. Part A evaluated safety & efficacy of multiple 5 mg/50 µL doses of intravitreal (IVT) LFG316 against sham every 28 days for 505 days Part B evaluated the safety and pharmacokinetics of a single IVT dose of 10 mg/100 µL of LFG316 |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | LFG316 | Sham |
|---|---|---|
| Arm/Group Description | ||
| Period Title: Part A | ||
| STARTED | 99 | 51 |
| COMPLETED | 69 | 38 |
| NOT COMPLETED | 30 | 13 |
| Period Title: Part A | ||
| STARTED | 7 | 1 |
| COMPLETED | 6 | 1 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Part A- LFG316 5 mg | Part A- Sham | Part B- LFG316 10 mg | Part B- Sham | Total |
|---|---|---|---|---|---|
| Arm/Group Description | LFG316 5 mg injection every 28 days for a total of 12 injections | sham injection every 28 days for a total of 12 injections | Single LFG316 10 mg Injection | Single Sham injection | Total of all reporting groups |
| Overall Participants | 99 | 51 | 7 | 1 | 158 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
78.6
(7.5)
|
80.8
(6.5)
|
84.1
(3.8)
|
81.0
(NA)
|
79.4
(7.2)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
58
58.6%
|
32
62.7%
|
6
85.7%
|
1
100%
|
97
61.4%
|
| Male |
41
41.4%
|
19
37.3%
|
1
14.3%
|
0
0%
|
61
38.6%
|
Outcome Measures
| Title | Part A: Geographic Atrophy (GA) Lesion Growth Measured by Fundus Autofluorescence (FAF) From Baseline to Day 505 |
|---|---|
| Description | Geographic atrophy (GA) lesion growth measured by fundus autofluorescence (FAF) from baseline to Day 505. |
| Time Frame | Day 1 to Day 505 (starting from the day of first intravitreal injection until Day 505) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic analysis set (PD) which includes all patients with at least one dose of study drug and evaluable PD data. |
| Arm/Group Title | LFG316 | Sham |
|---|---|---|
| Arm/Group Description | LFG316 (5 mg/50 µL) | Sham injection |
| Measure Participants | 50 | 27 |
| Mean (Standard Deviation) [mm^2] |
1.95
(1.01)
|
1.58
(1.12)
|
| Title | Part A: Change From Baseline in GA Lesions Growth Measured by Fundus Autofluorescence |
|---|---|
| Description | Mean change in GA lesion growth from baseline to Day 169 and Day 505. |
| Time Frame | Day 1 to Day 169 and Day 505 (starting from the day of first intravitreal injection until Day 505) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Set which included patients who had at least one dose of study drug and had evaluable PD Data. |
| Arm/Group Title | LFG316 | Sham |
|---|---|---|
| Arm/Group Description | LFG316 (5 mg/50 µL) | Sham Injection |
| Measure Participants | 74 | 38 |
| Day 169 (n=68, 37) |
0.99
(0.60)
|
0.88
(0.77)
|
| Day 505 (n=38, 18) |
2.78
(1.28)
|
2.03
(1.00)
|
| Title | Part A: Change in Best Corrected Visual Acuity (BCVA) as Measured by the EDTRS (Early Treatment of Diabetic Retinopathy Study) Scale From Baseline to Days 169, 337 & 505 in Patients Receiving Every 28 Days, Successive IVT Doses of LFG316 Compared to Sham |
|---|---|
| Description | Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: STUDY |
| Time Frame | Baseline Day 1, Day 169, Day 337 to Day 505 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set which includes all patients with at least one dose of study drug and evaluable PD data. |
| Arm/Group Title | LFG316 | Sham |
|---|---|---|
| Arm/Group Description | LFG316 (5 mg/50 µL) | Sham Injection |
| Measure Participants | 74 | 38 |
| Baseline Day 1 (n=74, 38) |
43.91
(12.93)
|
40.26
(14.97)
|
| Day 169 (n=71, 36) |
48.38
(11.05)
|
42.50
(15.14)
|
| Day 337 (n=53, 30) |
47.49
(11.25)
|
42.97
(14.23)
|
| Day 505 (n=40, 23) |
44.73
(11.29)
|
43.78
(14.11)
|
| Title | Part A: Summary of Best Corrected Visual Acuity Over Time, Statistical Analysis of Change in Best Corrected Visual Acuity Over Time Parameter: Visual Acuity (EDTRS Letter) BCVA Scale is 0-100, Worst is 0 and Best 100 Eye: FELLOW |
|---|---|
| Description | Part A: Summary of best corrected visual acuity over time, statistical analysis of change in best corrected visual acuity over time Parameter: Visual Acuity (EDTRS letter) BCVA scale is 0-100, worst is 0 and best 100 Eye: FELLOW |
| Time Frame | Baseline Day 1, Day 169, Day 337 to Day 505 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set which includes all patients with at least one dose of study drug and evaluable PD data. |
| Arm/Group Title | LFG316 | Sham |
|---|---|---|
| Arm/Group Description | LFG316 (5 mg/50 µL) | Sham Injection |
| Measure Participants | 74 | 38 |
| Baseline Day 1 (n=74, 38) |
54.66
(22.02)
|
55.13
(18.27)
|
| Day 169 (n=71, 36) |
54.59
(21.92)
|
57.33
(17.89)
|
| Day 337 (n=53, 30) |
52.75
(21.66)
|
53.87
(18.83)
|
| Day 505 (n=40, 23) |
50.95
(20.67)
|
49.87
(19.35)
|
| Title | Part A: Concentrations of Total LFG316 in Blood During the Course of the Study |
|---|---|
| Description | Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=hours after the last administered dose e.g.; 0.0 means just before dosing. If the mean concentration is 0.00, that means there is no drug in the bloodstream |
| Time Frame | Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data. |
| Arm/Group Title | LFG316 |
|---|---|
| Arm/Group Description | LFG316 (5 mg/50 µL) |
| Measure Participants | 99 |
| Day 1 (n=99), h=0 |
0.00
(0.00)
|
| Day 1(n= 97), h= 24 |
293
(332)
|
| Day 1(n=91), h=336 |
560
(238)
|
| Day 29 (n=94), h=0 |
289
(214)
|
| Day 57 (n=96), h=0 |
382
(218)
|
| Day 85 (n=93), h=0 |
436
(210)
|
| Day 113 (n=83), h=0 |
433
(219)
|
| Day 141 (n=84), h=0 |
451
(218)
|
| Day 141 (n=9), h=672 |
482
(174)
|
| Day 169 (n=68), h=0 |
446
(204)
|
| Day 197 (n=73), h=0 |
434
(231)
|
| Day 225 (n=71), h=0 |
471
(224)
|
| Day 253 (n=42), h=0 |
465
(237)
|
| Day 281 (n=69), h=0 |
485
(274)
|
| Day 309 (n=68), h=0 |
447
(226)
|
| Day 309 (n=22), h=672 |
405
(189)
|
| Day 365 (n=40), h=0 |
427
(288)
|
| Day 393 (n=42), h=0 |
464
(239)
|
| Day 421(n=40), h=0 |
471
(228)
|
| Day 449 (n=40), h=0 |
459
(214)
|
| Day 477 (n=39), h=0 |
422
(236)
|
| Day 477 (n=41), h=672 |
439
(191)
|
| Day 477 (n=38), h=1968 |
0.00
(0.00)
|
| Day 309 (n=16), h=2688 |
0.00
(0.00)
|
| Day 337 (n=42), h=0 |
435
(283)
|
| Title | Part A: Concentrations of Total C5 in Blood During the Course of the Study |
|---|---|
| Description | Summary statistic of total C5 concentrations n=number of participants, h=scheduled sampling time |
| Time Frame | Day 1 to Day 559 (starting from the day of first intravitreal injection to day 559) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Analysis includes patients who received at least one dose of study drug with evaluable PD data. |
| Arm/Group Title | LFG316 | Sham |
|---|---|---|
| Arm/Group Description | LFG316 (5 mg/50 µL) | Sham injection |
| Measure Participants | 99 | 51 |
| Day 1 (n=99, 51), h=0 |
147000
(28900)
|
142000
(25500)
|
| (n= 97, 51), h= 24 |
143000
(31200)
|
139000
(27600)
|
| (n=91, 49), h=336 |
149000
(41100)
|
136000
(25600)
|
| Day 29 (n=94, 47), h=0 |
145000
(31200)
|
142000
(33900)
|
| Day 57 (n=96, 49), h=0 |
147000
(29300)
|
148000
(40400)
|
| Day 85 (n=93, 46), h=0 |
154000
(42500)
|
144000
(39100)
|
| Day 113 (n=83, 49), h=0 |
153000
(46200)
|
146000
(42100)
|
| Day 141 (n=84, 45), h=0 |
144000
(32600)
|
141000
(25600)
|
| (n=9, 3), h=672 |
146000
(288000)
|
135000
(8000)
|
| Day 169 (n=68, 37), h=0 |
147000
(39400)
|
144000
(38600)
|
| Day 197 (n=73, 36), h=0 |
143000
(27300)
|
139000
(32500)
|
| Day 225 (n=71, 34), h=0 |
152000
(51600)
|
140000
(33600)
|
| Day 253 (n=42, 18), h=0 |
144000
(38500)
|
129000
(31000)
|
| Day 281 (n=69, 34), h=0 |
145000
(28000)
|
144000
(35300)
|
| Day 309 (n=68, 32), h=0 |
151000
(45200)
|
148000
(39400)
|
| (n=22, 12), h=672 |
137000
(31000)
|
145000
(33200)
|
| Day 365 (n=40, 24), h=0 |
146000
(29300)
|
131000
(29300)
|
| Day 393 (n=42, 22), h=0 |
145000
(23700)
|
132000
(28500)
|
| Day 421(n=40, 22), h=0 |
149000
(24700)
|
141000
(34200)
|
| Day 449 (n=40, 23), h=0 |
160000
(41200)
|
144000
(27000)
|
| Day 477 (n=39, 21), h=0 |
148000
(20400)
|
156000
(53900)
|
| (n=41, 21), h=672 |
158000
(37800)
|
155000
(59000)
|
| (n=38, 22), h=1968 |
198000
(82700)
|
186000
(79600)
|
| Day 309 (n=16, 10), h=2688 |
135000
(19600)
|
135000
(18800)
|
| Day 337 (n=44, 24), h-0 |
147000
(27900)
|
137000
(36200)
|
| Title | Part A: Sensitivity Analysis of the Primary End Point: Mixed Effects Model for Repeated Measurements on GA Lesion Growth Measured by Fundus Autoflourescence |
|---|---|
| Description | Number is the Estimated Difference (95% CI) in lesion size. |
| Time Frame | The primary objective was from Day 1 to Day 337, however data was captured to Day 505 as exploratory objective |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD Set which included patients who had at least one dose of study drug and had evaluable PD Data. |
| Arm/Group Title | LFG316 | Sham | LFG316 5 Mg-Sham |
|---|---|---|---|
| Arm/Group Description | LFG316 (5 mg/50 µL) | Difference in mean between LFG316 arm and Sham arm. | |
| Measure Participants | 50 | 27 | 77 |
| Bilateral Day 169 |
0.975
|
0.913
|
0.062
|
| Bilateral Day 337 |
1.825
|
1.710
|
0.115
|
| Bilateral Day 505 |
2.674
|
2.506
|
0.168
|
| Overall Day 169 |
1.036
|
0.937
|
0.099
|
| Overall Day 337 |
1.885
|
1.734
|
0.152
|
| Overall Day 505 |
2.735
|
2.530
|
0.205
|
| Title | Part B: AUC (Area Under the Curve) - Summary Statistics for PK Parameters |
|---|---|
| Description | Summary statistic of total LFG316 concentrations (pharmacokinetic analysis set) n=number of participants, h=scheduled sampling time |
| Time Frame | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data. |
| Arm/Group Title | LFG316 |
|---|---|
| Arm/Group Description | LFG316 (10 mg/100 µL) |
| Measure Participants | 7 |
| AUCall (hr*ng/mL) |
743000
(241000)
|
| AUClast (hr*ng/mL) |
600000
(212000)
|
| Title | Part B: Safety and Tolerability of a Single Intravitreal (IVT) Dose of 10 mg/100 μL of LFG316 in Patients With Advanced AMD). |
|---|---|
| Description | This primary outcome (for Part B) is reported under the Adverse Events section. |
| Time Frame | Day 1 to Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part A - LFG316 5mg | Sham - Part A | Part B - LFG316 10mg | Sham - Part B |
|---|---|---|---|---|
| Arm/Group Description | Part A - LFG316 5 mg/50 µL injection every 4 weeks for 18 months | sham injection every 4 weeks for a total of 18 injections | Part B - LFG316 10 mg/100 µL injection every 4 weeks for 18 months | Single sham injection |
| Measure Participants | 99 | 51 | 7 | 1 |
| Total # Affected by any Serious Adverse Event |
27
|
11
|
1
|
0
|
| Total # at Risk by any Serious Adverse Event |
99
|
51
|
7
|
1
|
| Title | Tmax (hr) |
|---|---|
| Description | PART B: Tmax (Time of Maximum concentration observed) This is the highest concentration of drug in the blood that is measured after a dose. Cmax usually happens within a few hours after the dose is taken. The time that Cmax happens is referred to as Tmax. For some antiretroviral drugs, a high Cmax is thought to increase the risk of side effects from the drug. |
| Time Frame | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data. |
| Arm/Group Title | LFG316 |
|---|---|
| Arm/Group Description | LFG316 (10 mg/100 µL) |
| Measure Participants | 7 |
| Median (Full Range) [hours] |
213
|
| Title | Part B: Cmax - Summary Statistic for PK Parameters |
|---|---|
| Description | Summary statistic for Part B of total LFG316 concentrations (pharmacokinetic analysis set) Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose |
| Time Frame | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data. |
| Arm/Group Title | LFG316 |
|---|---|
| Arm/Group Description | LFG316 (10 mg/100 µL) |
| Measure Participants | 7 |
| Mean (Standard Deviation) [ng/mL] |
1010
(213)
|
| Title | Part B: Cmax_D - Summary Statistic for PK Parameters |
|---|---|
| Description | Cmax_D=ng/mL/mg |
| Time Frame | Day 1 to Day 85 (starting from the day of first intravitreal injection to day 85) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set: The PK analysis set included all patients with at least one dose of study drug and evaluable PK data. |
| Arm/Group Title | LFG316 |
|---|---|
| Arm/Group Description | LFG316 (10 mg/100 µL) |
| Measure Participants | 7 |
| Mean (Standard Deviation) [ng/mL/mg] |
101
(21.3)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Part A - LFG316 5mg | Part A - Sham | Part B - LFG316 10mg | Part B - Sham | ||||
| Arm/Group Description | Part A - LFG316 5 mg/50 µL injection every 4 weeks for 18 months | sham injection every 4 weeks for a total of 18 injections | Part B - Single LFG316 10 mg/100 µL injection | single sham injection | ||||
All Cause Mortality |
||||||||
| Part A - LFG316 5mg | Part A - Sham | Part B - LFG316 10mg | Part B - Sham | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Part A - LFG316 5mg | Part A - Sham | Part B - LFG316 10mg | Part B - Sham | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/99 (27.3%) | 11/51 (21.6%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Immune thrombocytopenic purpura | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 1/99 (1%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Atrial fibrillation | 1/99 (1%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Atrioventricular block second degree | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cardiac failure congestive | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cardiomyopathy | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Coronary artery disease | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vertigo | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye disorders | ||||||||
| Visual acuity reduced (Fellow Eye) | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual acuity reduced (Study Eye) | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain upper | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Constipation | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Gastrointestinal haemorrhage | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Gastrooesophageal reflux disease | 0/99 (0%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Small intestinal obstruction | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Umbilical hernia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Upper gastrointestinal haemorrhage | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vomiting | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| General disorders | ||||||||
| Non-cardiac chest pain | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Infections and infestations | ||||||||
| Cellulitis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Clostridium difficile infection | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cystitis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Endophthalmitis (Study Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pneumonia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urinary tract infection | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Auricular haematoma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hip fracture | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Lumbar vertebral fracture | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Investigations | ||||||||
| International normalised ratio increased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hyperlipidaemia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Muscular weakness | 1/99 (1%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Osteoarthritis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Bladder cancer | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Breast cancer | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Invasive ductal breast carcinoma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Myelodysplastic syndrome | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Plasma cell myeloma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Prostate cancer | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Rectal adenocarcinoma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Squamous cell carcinoma of lung | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Uterine cancer | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Transient ischaemic attack | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Psychiatric disorders | ||||||||
| Confusional state | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Delirium | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute prerenal failure | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haematuria | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urinary retention | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic obstructive pulmonary disease | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Lung consolidation | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pulmonary embolism | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haemorrhage | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hypertension | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Temporal arteritis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Part A - LFG316 5mg | Part A - Sham | Part B - LFG316 10mg | Part B - Sham | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 98/99 (99%) | 42/51 (82.4%) | 4/7 (57.1%) | 1/1 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 6/99 (6.1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Increased tendency to bruise | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Macrocytosis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Splenomegaly | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 2/99 (2%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Arrhythmia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Atrial fibrillation | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Bradycardia | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cardiac failure congestive | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Coronary artery disease | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Heart valve incompetence | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tachycardia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ventricular extrasystoles | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| Corneal dystrophy (Fellow Eye) | 0/99 (0%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Corneal dystrophy (Study Eye) | 0/99 (0%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Cerumen impaction | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ear pain | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vertigo | 2/99 (2%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Endocrine disorders | ||||||||
| Hypothyroidism | 4/99 (4%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye disorders | ||||||||
| Anterior chamber cell (Study Eye) | 3/99 (3%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Anterior chamber flare (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blepharitis (Fellow Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blepharitis (Study Eye) | 4/99 (4%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blepharitis allergic (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blepharospasm (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cataract (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cataract (Study Eye) | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cataract nuclear (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cataract nuclear (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cataract subcapsular (Fellow Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cataract subcapsular (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Charles Bonnet syndrome | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Charles Bonnet syndrome (Fellow Eye) | 0/99 (0%) | 1/51 (2%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Charles Bonnet syndrome (Study Eye) | 0/99 (0%) | 1/51 (2%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Chorioretinal atrophy (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Chorioretinal atrophy (Study Eye) | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Choroidal neovascularisation (Fellow Eye) | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Choroidal neovascularisation (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Conjunctival haemorrhage (Fellow Eye) | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Conjunctival haemorrhage (Study Eye) | 70/99 (70.7%) | 29/51 (56.9%) | 2/7 (28.6%) | 0/1 (0%) | ||||
| Conjunctival hyperaemia (Study Eye) | 3/99 (3%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Conjunctival oedema (Study Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Conjunctival vascular disorder (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Corneal deposits (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Corneal oedema (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Corneal opacity (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Corneal scar (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Diplopia (Fellow Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Diplopia (Study Eye) | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dry eye (Fellow Eye) | 5/99 (5.1%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dry eye (Study Eye) | 5/99 (5.1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ectropion (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Erythema of eyelid (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Exfoliation glaucoma (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye colour change (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye inflammation (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye irritation (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye irritation (Study Eye) | 11/99 (11.1%) | 5/51 (9.8%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye pain (Fellow Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye pain (Study Eye) | 12/99 (12.1%) | 6/51 (11.8%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye pruritus (Fellow Eye) | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye pruritus (Study Eye) | 4/99 (4%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye swelling (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eyelid irritation (Study Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eyelid oedema (Study Eye) | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eyelids pruritus (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Foreign body sensation in eyes (Study Eye) | 10/99 (10.1%) | 7/51 (13.7%) | 0/7 (0%) | 0/1 (0%) | ||||
| Glaucoma (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Glaucoma (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hyphaema (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Iritis (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Keratitis (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Lacrimation decreased (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Lacrimation increased (Study Eye) | 6/99 (6.1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Macular degeneration (Fellow Eye) | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Macular oedema (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Neovascular age-related macular degeneration (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Neovascular age-related macular degeneration (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ocular discomfort (Study Eye) | 4/99 (4%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ocular hyperaemia (Study Eye) | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Optic disc disorder (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Optic disc haemorrhage (Fellow Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Photophobia (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Photophobia (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Photopsia (Study Eye) | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Posterior capsule opacification (Fellow Eye) | 4/99 (4%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Posterior capsule opacification (Study Eye) | 3/99 (3%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pterygium (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Punctate keratitis (Study Eye) | 4/99 (4%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Refraction disorder (Fellow Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Refraction disorder (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Retinal haemorrhage (Fellow Eye) | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Retinal haemorrhage (Study Eye) | 1/99 (1%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Retinal pigment epitheliopathy (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Retinal pigment epitheliopathy (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Retinal tear (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Scleral hyperaemia (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Subretinal fluid (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Trichiasis (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ulcerative keratitis (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Uveitis (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vision blurred (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vision blurred (Study Eye) | 1/99 (1%) | 3/51 (5.9%) | 0/7 (0%) | 1/1 (100%) | ||||
| Visual acuity reduced (Fellow Eye) | 3/99 (3%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual acuity reduced (Study Eye) | 7/99 (7.1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual acuity reduced transiently (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual acuity reduced transiently (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual brightness (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual brightness (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual impairment (Study Eye) | 3/99 (3%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous detachment | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous detachment (Fellow Eye) | 1/99 (1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous detachment (Study Eye) | 10/99 (10.1%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous disorder (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous floaters (Fellow Eye) | 3/99 (3%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous floaters (Study Eye) | 24/99 (24.2%) | 1/51 (2%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Vitreous haemorrhage (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous haemorrhage (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vitreous opacities (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 2/99 (2%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Abdominal pain upper | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Aphthous stomatitis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Constipation | 6/99 (6.1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Diarrhoea | 4/99 (4%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dyspepsia | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Gastric ulcer | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Gastrooesophageal reflux disease | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haematemesis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nausea | 9/99 (9.1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Oesophagitis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Small intestinal perforation | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tooth deposit | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Toothache | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vomiting | 5/99 (5.1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| General disorders | ||||||||
| Application site pain (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Asthenia | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Chest discomfort | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Chills | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Facial pain | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Fatigue | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Fibrosis (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Injection site bruising (Study Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Injection site erythema (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Injection site irritation (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Injection site reaction (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Non-cardiac chest pain | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Oedema peripheral | 6/99 (6.1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pain | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Peripheral swelling | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pyrexia | 1/99 (1%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Immune system disorders | ||||||||
| Allergy to arthropod bite | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Allergy to chemicals | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Drug hypersensitivity | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hypersensitivity | 4/99 (4%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Seasonal allergy | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Infections and infestations | ||||||||
| Acute sinusitis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Bronchitis | 8/99 (8.1%) | 4/51 (7.8%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cellulitis | 3/99 (3%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Conjunctivitis (Fellow Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Conjunctivitis (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cystitis | 3/99 (3%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Diverticulitis | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ear infection | 2/99 (2%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye infection staphylococcal (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Fungal skin infection | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Furuncle | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Herpes zoster | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hordeolum (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Influenza | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Kidney infection | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Laryngitis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Localised infection | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nasopharyngitis | 9/99 (9.1%) | 4/51 (7.8%) | 0/7 (0%) | 0/1 (0%) | ||||
| Onychomycosis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Oral candidiasis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Otitis media acute | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Paronychia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Periodontitis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pharyngitis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pneumonia | 2/99 (2%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Respiratory tract infection | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Rhinitis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Sinusitis | 3/99 (3%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tooth abscess | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tooth infection | 0/99 (0%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Upper respiratory tract infection | 13/99 (13.1%) | 4/51 (7.8%) | 0/7 (0%) | 1/1 (100%) | ||||
| Urinary tract infection | 3/99 (3%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urinary tract infection enterococcal | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Wound infection | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 2/99 (2%) | 3/51 (5.9%) | 0/7 (0%) | 1/1 (100%) | ||||
| Corneal abrasion (Study Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Fall | 6/99 (6.1%) | 3/51 (5.9%) | 0/7 (0%) | 1/1 (100%) | ||||
| Hand fracture | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Humerus fracture | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Joint injury | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Laceration | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ligament sprain | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Muscle injury | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Muscle strain | 0/99 (0%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Post procedural complication (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Post procedural discomfort (Study Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Post-traumatic pain | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Procedural headache | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Procedural pain | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Procedural pain (Study Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Rib fracture | 3/99 (3%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Skin abrasion | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Skin injury | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Spinal compression fracture | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Thermal burn | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tooth fracture | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Wound | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Investigations | ||||||||
| Blood cholesterol increased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blood creatinine increased | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blood glucose increased | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blood pressure increased | 1/99 (1%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blood triglycerides increased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Blood urea increased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cardiac murmur | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Crystal urine present | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Electrocardiogram T wave abnormal | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Glomerular filtration rate decreased | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haematocrit decreased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haemoglobin decreased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haemoglobin increased | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Heart rate irregular | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Intraocular pressure increased (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Intraocular pressure increased (Study Eye) | 4/99 (4%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Red blood cell count decreased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Red blood cell count increased | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Red blood cells urine | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Transaminases increased | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urine leukocyte esterase positive | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual acuity tests abnormal (Study Eye) | 0/99 (0%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Weight decreased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| White blood cell count decreased | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| White blood cells urine positive | 0/99 (0%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Diabetes mellitus | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Gout | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hypercholesterolaemia | 1/99 (1%) | 0/51 (0%) | 1/7 (14.3%) | 0/1 (0%) | ||||
| Hyperglycaemia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hyperlipidaemia | 3/99 (3%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hypokalaemia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hyponatraemia | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Type 2 diabetes mellitus | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 2/99 (2%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Arthritis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Back pain | 3/99 (3%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Chondrocalcinosis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Fibromyalgia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Foot deformity | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Fracture pain | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Musculoskeletal pain | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Musculoskeletal stiffness | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Neck pain | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Osteopenia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Osteoporotic fracture | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pain in extremity | 4/99 (4%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Spinal column stenosis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tendon pain | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tendonitis | 1/99 (1%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Trigger finger | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Basal cell carcinoma | 2/99 (2%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Benign breast neoplasm | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Benign neoplasm of eyelid (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Breast cancer | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eye naevus (Fellow Eye) | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Lipoma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Malignant melanoma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Squamous cell carcinoma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Squamous cell carcinoma of skin | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 6/99 (6.1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dysaesthesia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Head discomfort | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Headache | 5/99 (5.1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hyporeflexia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Lumbar radiculopathy | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Memory impairment | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nerve compression | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Neuropathy peripheral | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Presyncope | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Sciatica | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Sinus headache | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Visual field defect (Fellow Eye) | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Insomnia | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Mental status changes | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Bladder outlet obstruction | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Calculus bladder | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Chronic kidney disease | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dysuria | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haematuria | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nephrolithiasis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nocturia | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pelvi-ureteric obstruction | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Proteinuria | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urethral stenosis | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urinary incontinence | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urinary retention | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urinary tract pain | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Calculus prostatic | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Prostatic calcification | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Prostatic haemorrhage | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Prostatomegaly | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vaginal haemorrhage | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory failure | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Allergic cough | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Chronic obstructive pulmonary disease | 1/99 (1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cough | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dysphonia | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dyspnoea | 3/99 (3%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Epistaxis | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hypoxia | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Nasal congestion | 0/99 (0%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Oropharyngeal pain | 2/99 (2%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Pleural effusion | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Productive cough | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Respiratory failure | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Respiratory tract congestion | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Rhinorrhoea | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Sinus congestion | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Tracheomalacia | 0/99 (0%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Actinic keratosis | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cold sweat | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cutis laxa (Fellow Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Cutis laxa (Study Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dermatitis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dermatitis contact | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Dry skin | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Ecchymosis (Study Eye) | 2/99 (2%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Eczema | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Precancerous skin lesion | 0/99 (0%) | 2/51 (3.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Rash | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Urticaria | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Haematoma | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hypertension | 9/99 (9.1%) | 3/51 (5.9%) | 0/7 (0%) | 0/1 (0%) | ||||
| Hypotension | 1/99 (1%) | 1/51 (2%) | 0/7 (0%) | 0/1 (0%) | ||||
| Labile hypertension | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
| Poor peripheral circulation | 1/99 (1%) | 0/51 (0%) | 0/7 (0%) | 0/1 (0%) | ||||
Limitations/Caveats
Study conducted in 2 parts, Part A (n=150) & Part B (n=8). Total participants is 158
Primary Outcome for Part B is Safety and Tolerability as presented in the Adverse events section of this report
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01527500
Other Study ID Numbers:
- CLFG316A2203
First Posted:
Feb 7, 2012
Last Update Posted:
Jan 5, 2021
Last Verified:
Mar 1, 2019