Trial Outcomes & Findings for Safety and Efficacy of Ranibizumab in Japanese Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration (NCT NCT00284089)
NCT ID: NCT00284089
Last Updated: 2011-02-24
Results Overview
The efficacy assessment was based on Group B patients. Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
88 participants
Primary outcome timeframe
Baseline and Month 6
Results posted on
2011-02-24
Participant Flow
In total, 88 patients were enrolled in the study, 12 in Group A and 76 in Group B. The single dose phase of the study (Group A patients only) was completed prior to initiation of the multiple dose phase (Groups A and B).
Participant milestones
| Measure |
Group A: Ranibizumab 0.3 mg
In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.3 mg of ranibizumab once a month for an additional 11 months. Subsequently patients enrolling in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.70 years.
|
Group A: Ranibizumab 0.5 mg
In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.5 mg of ranibizumab once a month for an additional 11 months. Subsequently Group A patients enrolling in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.93 years.
|
Group B: Ranibizumab 0.3 mg
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
|
Group B: Ranibizumab 0.5 mg
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
|
|---|---|---|---|---|
|
Single Dose Phase
STARTED
|
6
|
6
|
0
|
0
|
|
Single Dose Phase
COMPLETED
|
6
|
6
|
0
|
0
|
|
Single Dose Phase
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Multiple Dose Phase
STARTED
|
5
|
6
|
35
|
41
|
|
Multiple Dose Phase
COMPLETED
|
4
|
6
|
31
|
37
|
|
Multiple Dose Phase
NOT COMPLETED
|
1
|
0
|
4
|
4
|
|
Extension Phase
STARTED
|
3
|
6
|
28
|
33
|
|
Extension Phase
COMPLETED
|
1
|
6
|
22
|
21
|
|
Extension Phase
NOT COMPLETED
|
2
|
0
|
6
|
12
|
Reasons for withdrawal
| Measure |
Group A: Ranibizumab 0.3 mg
In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.3 mg of ranibizumab once a month for an additional 11 months. Subsequently patients enrolling in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.70 years.
|
Group A: Ranibizumab 0.5 mg
In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.5 mg of ranibizumab once a month for an additional 11 months. Subsequently Group A patients enrolling in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.93 years.
|
Group B: Ranibizumab 0.3 mg
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
|
Group B: Ranibizumab 0.5 mg
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
|
|---|---|---|---|---|
|
Multiple Dose Phase
Adverse Event
|
1
|
0
|
1
|
1
|
|
Multiple Dose Phase
Protocol Violation
|
0
|
0
|
1
|
0
|
|
Multiple Dose Phase
Withdrawal by Subject
|
0
|
0
|
1
|
2
|
|
Multiple Dose Phase
Death
|
0
|
0
|
1
|
1
|
|
Extension Phase
Adverse Event
|
0
|
0
|
2
|
2
|
|
Extension Phase
condition no longer requires study drug
|
2
|
0
|
2
|
7
|
|
Extension Phase
Protocol Violation
|
0
|
0
|
1
|
0
|
|
Extension Phase
Withdrawal by Subject
|
0
|
0
|
1
|
3
|
Baseline Characteristics
Safety and Efficacy of Ranibizumab in Japanese Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration
Baseline characteristics by cohort
| Measure |
Group A: Ranibizumab 0.3 mg
n=6 Participants
In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.3 mg of ranibizumab once a month for an additional 11 months. Subsequently patients enrolling in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.70 years.
|
Group A: Ranibizumab 0.5 mg
n=6 Participants
In the single dose phase, all patients randomized in Group A received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye. Those patients who successfully completed this phase entered the multiple dose phase, where they received an intravitreal injection of 0.5 mg of ranibizumab once a month for an additional 11 months. Subsequently Group A patients enrolling in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.93 years.
|
Group B: Ranibizumab 0.3 mg
n=35 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients enrolled in the extension phase received an intravitreal injection of 0.3 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
|
Group B: Ranibizumab 0.5 mg
n=41 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study. Group B patients who enrolled in the extension phase received an intravitreal injection of 0.5 mg of ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
50 to <65 years
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=31 Participants
|
|
Age, Customized
65 to <75 years
|
1 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
29 Participants
n=31 Participants
|
|
Age, Customized
75 to <85 years
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
21 Participants
n=31 Participants
|
|
Age, Customized
>= 85 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
19 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
33 Participants
n=7 Participants
|
69 Participants
n=31 Participants
|
|
Gender
Female
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
9 participants
n=206 Participants
|
5 participants
n=7 Participants
|
15 participants
n=31 Participants
|
|
Gender
Male
|
3 participants
n=99 Participants
|
5 participants
n=107 Participants
|
19 participants
n=206 Participants
|
28 participants
n=7 Participants
|
55 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Baseline and Month 6Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. The Last Observation Carried Forward (LOCF) was used to impute missing data at month 6 in the ITT analysis.
The efficacy assessment was based on Group B patients. Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=35 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=41 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B
Baseline
|
47.6 Number of Letters
Standard Deviation 11.82
|
48.1 Number of Letters
Standard Deviation 10.75
|
|
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B
Month 6
|
55.7 Number of Letters
Standard Deviation 13.16
|
57.1 Number of Letters
Standard Deviation 14.99
|
|
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 6 in Group B
Change from Baseline
|
8.1 Number of Letters
Standard Deviation 12.65
|
9.0 Number of Letters
Standard Deviation 9.62
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment of the efficacy variable. The Last Observation carried Forward (LOCF) was used to impute missing data at month 12 in the ITT analysis.
The efficacy assessment was based on Group B patients. BCVA was assessed during all study visits using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=35 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=41 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B
Baseline
|
47.6 Number of Letters
Standard Deviation 11.82
|
48.1 Number of Letters
Standard Deviation 10.75
|
|
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B
Month 12
|
57.1 Number of Letters
Standard Deviation 12.91
|
58.6 Number of Letters
Standard Deviation 15.44
|
|
Mean Change From Baseline in the Best Corrected Visual Acuity Score of the Study Eye at Month 12 in Group B
Change from Baseline
|
9.5 Number of Letters
Standard Deviation 12.79
|
10.5 Number of Letters
Standard Deviation 11.14
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: ITT population, using LOCF.
BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters.
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=35 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=41 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Visual acuity < 34 letters at Month 12
|
2 Participants
|
1 Participants
|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Loss of < 15 letters from Baseline at month 6
|
34 Participants
|
41 Participants
|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Loss of < 15 letters from Baseline at month 12
|
34 Participants
|
41 Participants
|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Gain of ≥15 letters from Baseline at month 6
|
12 Participants
|
10 Participants
|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Gain of ≥15 letters from Baseline at month 12
|
13 Participants
|
13 Participants
|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Loss of ≥30 letters from Baseline at month 6
|
0 Participants
|
0 Participants
|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Loss of ≥30 letters from Baseline at month 12
|
0 Participants
|
0 Participants
|
|
Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Month 6 and Month 12 in Group B
Visual acuity < 34 letters at Month 6
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Month 12 (start of extension phase) and last visit of extension phase. Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.Population: The analysis population included all enrolled patients in the extension phase. For the analysis of the results of the extension phase, all data are presented as observed. Patients must have values both at Month 12 and Last Visit to be included.
Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 2 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 2 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=28 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=33 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B.
Baseline
|
47.9 Letters
Standard Deviation 12.59
|
50.0 Letters
Standard Deviation 10.38
|
|
Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B.
Month 12
|
59.1 Letters
Standard Deviation 11.69
|
59.8 Letters
Standard Deviation 15.07
|
|
Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B.
Last visit
|
55.4 Letters
Standard Deviation 17.14
|
57.6 Letters
Standard Deviation 15.36
|
|
Extension Phase: Mean Change From Month 12 (Start of Extension Phase) in Best Corrected Visual Acuity Score of the Study Eye at Last Visit of Extension Phase in Group B.
Change from Month 12
|
-3.6 Letters
Standard Deviation 14.82
|
-2.2 Letters
Standard Deviation 7.92
|
SECONDARY outcome
Timeframe: Baseline and last visit of extension phase - Duration in the extension phase varied depending on the study entry. The mean duration of treatment was 1.45 years in the 0.3 mg group and 1.36 years in the 0.5 mg dose group.Population: Includes patients enrolled in the extension phase, observed data.
BCVA measurements were taken in a sitting position using best correction determined from protocol refraction and ETDRS-like visual acuity testing charts at a starting test distance of 2 meters. The following categories were evaluated: * Participants with a BCVA score loss of fewer than 15 letters from baseline at Last Visit * Participants with a BCVA score loss of 30 or more letters from baseline at Last Visit * Participants with a BCVA score gain of 15 or more letters from baseline at Last Visit * Participants with a BCVA score of less than 34 letters at Last Visit
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=28 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=33 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B
Visual acuity < 34 letters
|
3 Participants
|
1 Participants
|
|
Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B
Loss of < 15 letters from Baseline
|
24 Participants
|
32 Participants
|
|
Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B
Gain of ≥15 letters from Baseline
|
9 Participants
|
9 Participants
|
|
Extension Phase: Categorical Analysis of Best Corrected Visual Acuity of the Study Eye at Last Visit of Extension Phase in Group B
Loss of ≥30 letters from Baseline
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, Months 3, 6, 9 and 12Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment. The Last Observation Carried Forward (LOCF) was used to impute missing data.
Choroidal Neovascularization was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The area of Choroidal Neovascularization is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm\^2 on the retina).
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=35 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=41 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
Mean change from Baseline at Month 6 [N=34, 40]
|
-0.15 disc areas
Standard Deviation 0.97
|
0.04 disc areas
Standard Deviation 0.76
|
|
Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
Baseline [N=35, 41]
|
2.11 disc areas
Standard Deviation 1.10
|
2.03 disc areas
Standard Deviation 1.66
|
|
Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
Mean change from Baseline at Month 3 [N=34, 40]
|
-0.10 disc areas
Standard Deviation 0.95
|
0.13 disc areas
Standard Deviation 0.75
|
|
Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
Mean change from Baseline at Month 9 [N=34, 40]
|
-0.23 disc areas
Standard Deviation 0.97
|
0.21 disc areas
Standard Deviation 0.90
|
|
Mean Change From Baseline in Total Area of Choroidal Neovascularization of the Study Eye in Group B
Mean change from Baseline at Month 12 [N=34, 40]
|
-0.16 disc areas
Standard Deviation 1.01
|
0.23 disc areas
Standard Deviation 1.08
|
SECONDARY outcome
Timeframe: Baseline, Months 3, 6, 9 and 12Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and had at least one post-baseline assessment. The Last Observation Carried Forward (LOCF) was used to impute missing data.
Area of leakage from CNV plus staining of retinal pigment epithelium was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed by the central reading center. The total area is expressed as Macular Photocoagulation Study standard Disc Areas (DA; equivalent to 2.54 mm\^2 on the retina).
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=35 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=41 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
Baseline [N=35, 41]
|
2.31 disc areas
Standard Deviation 1.17
|
2.49 disc areas
Standard Deviation 1.54
|
|
Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
Mean change from Baseline at Month 3 [N=34, 40]
|
-0.76 disc areas
Standard Deviation 0.85
|
-0.74 disc areas
Standard Deviation 1.21
|
|
Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
Mean change from Baseline at Month 6 [N=34, 40]
|
-1.21 disc areas
Standard Deviation 0.87
|
-1.10 disc areas
Standard Deviation 1.19
|
|
Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
Mean change from Baseline at Month 9 [N=34, 40]
|
-1.39 disc areas
Standard Deviation 1.02
|
-1.26 disc areas
Standard Deviation 1.45
|
|
Mean Change From Baseline in Total Area of Leakage From CNV Plus Staining of Retinal Pigment Epithelium of the Study Eye in Group B
Mean change from Baseline at Month 12 [N=34, 40]
|
-1.50 disc areas
Standard Deviation 1.08
|
-1.39 disc areas
Standard Deviation 1.48
|
SECONDARY outcome
Timeframe: Months 3, 6, 9 and 12Population: Intent-to treat (ITT) population for Group B patients consisted of all patients randomized in Group B that received at least one dose of study drug and for whom data was available. The Last Observation Carried Forward (LOCF) was used to impute missing data.
Area of leakage was assessed by fluorescein angiography in conjunction with color fundus photography. Analysis was performed at the central reading center.
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=34 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=40 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12.
Month 3
|
2.9 Percentage of participants
|
7.5 Percentage of participants
|
|
Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12.
Month 6
|
8.8 Percentage of participants
|
15.0 Percentage of participants
|
|
Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12.
Month 9
|
26.5 Percentage of participants
|
25.0 Percentage of participants
|
|
Percentage of Participants in Group B With Absence of Leakage in the Study Eye at Month 3, 6, 9 and 12.
Month 12
|
35.3 Percentage of participants
|
35.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Months 3, 6, 9 and 12Population: The analysis includes Group B Intent-to treat (ITT) population, observed data. OCT was performed in a total of 58 patients at selected sites.
Foveal retinal thickness was assessed by Optical Coherence Tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=28 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=30 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
Baseline [N=28, 30]
|
336.7 micrometers
Standard Deviation 195.3
|
370.7 micrometers
Standard Deviation 171.9
|
|
Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
Mean change from Baseline at Month 3 [N=27, 29]
|
-124.4 micrometers
Standard Deviation 141.6
|
-195.6 micrometers
Standard Deviation 187.5
|
|
Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
Mean change from Baseline at Month 6 [N=26, 28]
|
-142.9 micrometers
Standard Deviation 199.3
|
-225.6 micrometers
Standard Deviation 192.2
|
|
Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
Mean change from Baseline at Month 9 [N=26, 27]
|
-188.4 micrometers
Standard Deviation 190.1
|
-245.4 micrometers
Standard Deviation 203.1
|
|
Mean Change From Baseline in Foveal Retinal Thickness of the Study Eye in Group B
Mean change from Baseline at Month 12 [N=26, 26]
|
-194.0 micrometers
Standard Deviation 199.8
|
-257.8 micrometers
Standard Deviation 209.8
|
SECONDARY outcome
Timeframe: Baseline, Months 3, 6, 9 and 12Population: OCT was performed in a total of 58 patients at selected sites. Group B Intent-to treat (ITT) population, observed data only are included. The assessed sample size was small for total retinal volume data because the central reading center judged "Can not grade" due to retinal pigment epithelium disruption associated with CNV secondary to AMD.
Total retinal volume was assessed by Optical Coherence tomography (OCT) at a subset of the study sites and was analyzed by the central reading center.
Outcome measures
| Measure |
Group B: Ranibizumab 0.3 mg
n=28 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
Group B: Ranibizumab 0.5 mg
n=30 Participants
Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye in the multiple dose phase of the study.
|
|---|---|---|
|
Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
Baseline [N=11, 11]
|
7.23 micrometers
Standard Deviation 0.84
|
7.36 micrometers
Standard Deviation 0.97
|
|
Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
Mean change from Baseline at Month 3 [N=7, 7]
|
-0.78 micrometers
Standard Deviation 0.74
|
-0.67 micrometers
Standard Deviation 0.71
|
|
Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
Mean change from Baseline at Month 6 [N=6, 6]
|
-0.52 micrometers
Standard Deviation 0.60
|
-0.92 micrometers
Standard Deviation 0.96
|
|
Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
Mean change from Baseline at Month 9 [N=4, 5]
|
-0.48 micrometers
Standard Deviation 0.03
|
-0.28 micrometers
Standard Deviation 0.83
|
|
Mean Change From Baseline in Total Retinal Volume of the Study Eye in Group B
Mean change from Baseline at Month 12 [N=6, 6]
|
-0.95 micrometers
Standard Deviation 1.14
|
-0.42 micrometers
Standard Deviation 0.67
|
Adverse Events
Core Group A+B: Ranibizumab 0.3 mg
Serious events: 5 serious events
Other events: 38 other events
Deaths: 0 deaths
Core Group A+B: Ranibizumab 0.5 mg
Serious events: 8 serious events
Other events: 43 other events
Deaths: 0 deaths
Extension Group A+B: Ranibizumab 0.3 mg
Serious events: 5 serious events
Other events: 27 other events
Deaths: 0 deaths
Extension Group A+B: Ranibizumab 0.5 mg
Serious events: 8 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Core Group A+B: Ranibizumab 0.3 mg
n=41 participants at risk
"Core" means Single and Multiple Dose Phases. Group A patients received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye, followed by 11 additional intravitreal injections of 0.3 mg of ranibizumab once a month. Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye.
|
Core Group A+B: Ranibizumab 0.5 mg
n=47 participants at risk
"Core" means Single and Multiple Dose Phases. Group A patients received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye, followed by 11 additional intravitreal injections of 0.5 mg of ranibizumab once a month. Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye.
|
Extension Group A+B: Ranibizumab 0.3 mg
n=31 participants at risk
In the extension phase, enrolled patients received an intravitreal injection of 0.3 mg ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
|
Extension Group A+B: Ranibizumab 0.5 mg
n=39 participants at risk
In the extension phase, all patients received an intravitreal injection of 0.5 mg ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
|
|---|---|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Cataract (Fellow eye)
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Corneal oedema (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Eye pain (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Glaucomatocyclitic crises (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Macular degeneration (Fellow eye)
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Macular degeneration (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Retinal detachment (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Visual acuity reduced (Fellow eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Visual acuity reduced (Study eye)
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Visual acuity reduced transiently (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
4.3%
2/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Vitreous haemorrhage (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Gastrointestinal disorders
Enterocele
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Gastrointestinal disorders
Gastric polyps
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Infections and infestations
Abscess neck
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Injury, poisoning and procedural complications
Overdose (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
4.3%
2/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Investigations
Intraocular pressure increased (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
4.3%
2/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung carcinoma cell type unspecified recurrent
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Nervous system disorders
Ataxia
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Nervous system disorders
Spondylitic myelopathy
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Psychiatric disorders
Depression
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
Other adverse events
| Measure |
Core Group A+B: Ranibizumab 0.3 mg
n=41 participants at risk
"Core" means Single and Multiple Dose Phases. Group A patients received a single intravitreal injection of 0.3 mg of ranibizumab into the study eye, followed by 11 additional intravitreal injections of 0.3 mg of ranibizumab once a month. Group B patients received a total of 12 monthly intravitreal injections of 0.3 mg of ranibizumab into the study eye.
|
Core Group A+B: Ranibizumab 0.5 mg
n=47 participants at risk
"Core" means Single and Multiple Dose Phases. Group A patients received a single intravitreal injection of 0.5 mg of ranibizumab into the study eye, followed by 11 additional intravitreal injections of 0.5 mg of ranibizumab once a month. Group B patients received a total of 12 monthly intravitreal injections of 0.5 mg of ranibizumab into the study eye.
|
Extension Group A+B: Ranibizumab 0.3 mg
n=31 participants at risk
In the extension phase, enrolled patients received an intravitreal injection of 0.3 mg ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.45 years.
|
Extension Group A+B: Ranibizumab 0.5 mg
n=39 participants at risk
In the extension phase, all patients received an intravitreal injection of 0.5 mg ranibizumab according to an individualized flexible interval regimen guided by monthly best corrected visual acuity scores and other ophthalmic examinations. In the extension phase patients received the same dose level as they received in the multiple dose phase of the study, for an average of 1.36 years.
|
|---|---|---|---|---|
|
Eye disorders
Conjunctival haemorrhage (Study eye)
|
73.2%
30/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
59.6%
28/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
41.9%
13/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
35.9%
14/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Conjunctival hyperaemia (Study eye)
|
19.5%
8/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
17.0%
8/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.5%
2/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Conjunctivitis allergic (Fellow eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
5.1%
2/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Conjunctivitis allergic (Study eye)
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
5.1%
2/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Eye pain (Study eye)
|
22.0%
9/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
21.3%
10/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.5%
2/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Myodesopsia (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
7.7%
3/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Ocular hyperaemia (Study eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.4%
3/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Polypoidal choroidal vasculopathy (Fellow eye)
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.5%
2/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Punctate keratitis (Study eye)
|
17.1%
7/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
8.5%
4/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Retinal detachment (Study eye)
|
12.2%
5/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
4.3%
2/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.5%
2/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
12.8%
5/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Retinal haemorrhage (Fellow eye)
|
7.3%
3/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
10.6%
5/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
19.4%
6/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
5.1%
2/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Retinal haemorrhage (Study eye)
|
29.3%
12/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
10.6%
5/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
29.0%
9/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
25.6%
10/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Visual acuity reduced (Study eye)
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.4%
3/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Vitreous detachment (Study eye)
|
7.3%
3/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Eye disorders
Vitreous floaters (Study eye)
|
2.4%
1/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.4%
3/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Gastrointestinal disorders
Constipation
|
9.8%
4/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Gastrointestinal disorders
Dental caries
|
4.9%
2/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
5.1%
2/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Gastrointestinal disorders
Diarrhoea
|
4.9%
2/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.4%
3/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Gastrointestinal disorders
Nausea
|
7.3%
3/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.5%
2/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Infections and infestations
Nasopharyngitis
|
17.1%
7/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
21.3%
10/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
19.4%
6/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
23.1%
9/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
3.2%
1/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
5.1%
2/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Investigations
Intraocular pressure increased (Study eye)
|
4.9%
2/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
12.8%
6/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.5%
2/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
10.3%
4/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
4.3%
2/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
9.7%
3/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Nervous system disorders
Headache
|
9.8%
4/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.5%
2/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Reproductive system and breast disorders
Prostatomegaly
|
7.3%
3/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
5.1%
2/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Skin and subcutaneous tissue disorders
Eczema
|
7.3%
3/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
6.4%
3/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
0.00%
0/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
|
Vascular disorders
Hypertension
|
7.3%
3/41 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.1%
1/47 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
12.9%
4/31 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
2.6%
1/39 • The timeframe for the Core Phase (Single and Multiple Dose Phases) was 12 months. For the Extension Phase adverse event data was collected from Month 12 through to the Last Visit (the maximum time on study was 35 months total).
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862 778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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 (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER