Trial Outcomes & Findings for Phase II Combination Steroid and Anti-VEGF for Persistent DME (NCT NCT01945866)
NCT ID: NCT01945866
Last Updated: 2018-09-25
Results Overview
At 24 weeks after randomization, mean change in visual acuity letter score, adjusted for visual acuity at time of randomization
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
129 participants
Primary outcome timeframe
24 weeks after randomization
Results posted on
2018-09-25
Participant Flow
Phase 2 multi center randomized trial conducted at 40 US sites; 129 eyes (116 adults) with diabetes between February 2014 and December 2016. Participants with 2 study eyes enrolled one eye in each arm. Therefore, each arm includes no more than 1 study eye per participant; thus the number of eyes is equal to the number of participants in each arm.
A 12-week run-in phase was conducted to confirm that eyes with persistent diabetic macular edema (DME) still persisted after additional anti-vascular endothelial growth factor (VEGF) injections. At week 12 of the run-in phase, eyes that had received all run-in injections, and continued to meet specific criteria were eligible for randomization.
Unit of analysis: Eyes
Participant milestones
| Measure |
Sham + Intravitreal Ranibizumab 0.3 mg
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria. Dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
|---|---|---|
|
Overall Study
STARTED
|
65 65
|
64 64
|
|
Overall Study
COMPLETED
|
63 63
|
64 64
|
|
Overall Study
NOT COMPLETED
|
2 2
|
0 0
|
Reasons for withdrawal
| Measure |
Sham + Intravitreal Ranibizumab 0.3 mg
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria. Dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
|---|---|---|
|
Overall Study
Eyes did not complete or were dropped
|
2
|
0
|
Baseline Characteristics
Phase II Combination Steroid and Anti-VEGF for Persistent DME
Baseline characteristics by cohort
| Measure |
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Sham and ranibizumab, 0.3 mg, injections
|
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=65 Eyes
Combination of ranibizumab, 0.3 mg and intravitreous sustained dexamethasone drug-delivery system (Ozurdex; Allergan), 700 µg, injection
|
Total
n=129 Eyes
Total of all reporting groups
|
|---|---|---|---|
|
Arterial Blood Pressure
|
98 mmHg
n=14 Eyes
|
97 mmHg
n=23 Eyes
|
97 mmHg
n=50 Eyes
|
|
Smoking status
Never
|
43 Eyes
n=14 Eyes
|
44 Eyes
n=23 Eyes
|
87 Eyes
n=50 Eyes
|
|
Smoking status
Prior
|
14 Eyes
n=14 Eyes
|
18 Eyes
n=23 Eyes
|
32 Eyes
n=50 Eyes
|
|
Age, Customized
Age
|
66 years
n=14 Eyes
|
64 years
n=23 Eyes
|
65 years
n=50 Eyes
|
|
Sex/Gender, Customized
Women
|
36 Eyes
n=14 Eyes
|
31 Eyes
n=23 Eyes
|
67 Eyes
n=50 Eyes
|
|
Sex/Gender, Customized
Male
|
28 Eyes
n=14 Eyes
|
34 Eyes
n=23 Eyes
|
62 Eyes
n=50 Eyes
|
|
Race/Ethnicity, Customized
White
|
35 Eyes
n=14 Eyes
|
39 Eyes
n=23 Eyes
|
74 Eyes
n=50 Eyes
|
|
Race/Ethnicity, Customized
Black/African American
|
9 Eyes
n=14 Eyes
|
6 Eyes
n=23 Eyes
|
15 Eyes
n=50 Eyes
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
16 Eyes
n=14 Eyes
|
13 Eyes
n=23 Eyes
|
29 Eyes
n=50 Eyes
|
|
Race/Ethnicity, Customized
Asian
|
2 Eyes
n=14 Eyes
|
6 Eyes
n=23 Eyes
|
8 Eyes
n=50 Eyes
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Eyes
n=14 Eyes
|
0 Eyes
n=23 Eyes
|
1 Eyes
n=50 Eyes
|
|
Race/Ethnicity, Customized
Unknown/not reported
|
1 Eyes
n=14 Eyes
|
1 Eyes
n=23 Eyes
|
2 Eyes
n=50 Eyes
|
|
Diabetes Type
Type 1
|
2 Eyes
n=14 Eyes
|
2 Eyes
n=23 Eyes
|
4 Eyes
n=50 Eyes
|
|
Diabetes Type
Type 2
|
61 Eyes
n=14 Eyes
|
62 Eyes
n=23 Eyes
|
123 Eyes
n=50 Eyes
|
|
Diabetes Type
Uncertain
|
1 Eyes
n=14 Eyes
|
1 Eyes
n=23 Eyes
|
2 Eyes
n=50 Eyes
|
|
Duration of Diabetes
|
19 years
n=14 Eyes
|
15 years
n=23 Eyes
|
17 years
n=50 Eyes
|
|
Insulin Used
|
39 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Hemoglobin A1c
|
7.4 Percent Hemoglobin
n=14 Eyes
|
7.1 Percent Hemoglobin
n=23 Eyes
|
7.3 Percent Hemoglobin
n=50 Eyes
|
|
Smoking status
Current
|
7 Eyes
n=14 Eyes
|
3 Eyes
n=23 Eyes
|
10 Eyes
n=50 Eyes
|
|
Body Mass Index
|
33 kg/m˄2
n=14 Eyes
|
32 kg/m˄2
n=23 Eyes
|
32 kg/m˄2
n=50 Eyes
|
|
Participants with 2 study eyes
|
13 participants
n=14 Eyes
|
13 participants
n=23 Eyes
|
26 participants
n=50 Eyes
|
|
Prior macular laser treatment for DME
|
31 Eyes
n=14 Eyes
|
31 Eyes
n=23 Eyes
|
62 Eyes
n=50 Eyes
|
|
Prior Anti-VEGF for DME
Aflibercept only
|
8 Eyes
n=14 Eyes
|
7 Eyes
n=23 Eyes
|
15 Eyes
n=50 Eyes
|
|
Prior Anti-VEGF for DME
Bevacizumab only
|
49 Eyes
n=14 Eyes
|
48 Eyes
n=23 Eyes
|
97 Eyes
n=50 Eyes
|
|
Prior Anti-VEGF for DME
Ranibizumab only
|
6 Eyes
n=14 Eyes
|
3 Eyes
n=23 Eyes
|
9 Eyes
n=50 Eyes
|
|
Prior Anti-VEGF for DME
Both aflibercept and bevacizumab
|
0 Eyes
n=14 Eyes
|
4 Eyes
n=23 Eyes
|
4 Eyes
n=50 Eyes
|
|
Prior Anti-VEGF for DME
Both aflibercept and ranibizumab
|
0 Eyes
n=14 Eyes
|
1 Eyes
n=23 Eyes
|
1 Eyes
n=50 Eyes
|
|
Prior Anti-VEGF for DME
Both bevacizumab and ranibizumab
|
1 Eyes
n=14 Eyes
|
2 Eyes
n=23 Eyes
|
3 Eyes
n=50 Eyes
|
|
Total anti-VEGF injections for DME within the 20 weeks before run-in phase
|
3 Injections
n=14 Eyes
|
3 Injections
n=23 Eyes
|
3 Injections
n=50 Eyes
|
|
Randomization visual acuity letter score
|
63 units on a scale
STANDARD_DEVIATION 13 • n=14 Eyes
|
63 units on a scale
STANDARD_DEVIATION 12 • n=23 Eyes
|
63 units on a scale
STANDARD_DEVIATION 12 • n=50 Eyes
|
|
Randomization central subfield thickness
|
396 Microns
STANDARD_DEVIATION 122 • n=14 Eyes
|
375 Microns
STANDARD_DEVIATION 97 • n=23 Eyes
|
385 Microns
STANDARD_DEVIATION 110 • n=50 Eyes
|
|
Change in central subfield thickness from enrollment to randomization
|
-50 Microns
STANDARD_DEVIATION 102 • n=14 Eyes
|
-58 Microns
STANDARD_DEVIATION 83 • n=23 Eyes
|
-54 Microns
STANDARD_DEVIATION 93 • n=50 Eyes
|
|
Improvement in visual acuity(VA) and OCT CST thickness during run-in phase
Neither VA nor OCT CST is improved
|
12 Eyes
n=14 Eyes
|
15 Eyes
n=23 Eyes
|
27 Eyes
n=50 Eyes
|
|
Improvement in visual acuity(VA) and OCT CST thickness during run-in phase
VA and OCT CST are both improved
|
22 Eyes
n=14 Eyes
|
22 Eyes
n=23 Eyes
|
44 Eyes
n=50 Eyes
|
|
Improvement in visual acuity(VA) and OCT CST thickness during run-in phase
VA is not improved but OCT CST is improved
|
16 Eyes
n=14 Eyes
|
16 Eyes
n=23 Eyes
|
32 Eyes
n=50 Eyes
|
|
Improvement in visual acuity(VA) and OCT CST thickness during run-in phase
VA is improved but OCT CST is not improved
|
14 Eyes
n=14 Eyes
|
12 Eyes
n=23 Eyes
|
26 Eyes
n=50 Eyes
|
|
Randomization retinal volume
|
8.6 mm3
STANDARD_DEVIATION 2.0 • n=14 Eyes
|
8.3 mm3
STANDARD_DEVIATION 1.6 • n=23 Eyes
|
8.5 mm3
STANDARD_DEVIATION 1.8 • n=50 Eyes
|
|
Randomization diabetic retinopathy severity level on clinical examination
Mild/moderate NPDR
|
28 Eyes
n=14 Eyes
|
30 Eyes
n=23 Eyes
|
58 Eyes
n=50 Eyes
|
|
Randomization diabetic retinopathy severity level on clinical examination
Severe NPDR
|
12 Eyes
n=14 Eyes
|
10 Eyes
n=23 Eyes
|
22 Eyes
n=50 Eyes
|
|
Randomization diabetic retinopathy severity level on clinical examination
PDR and/or prior scatter laser
|
24 Eyes
n=14 Eyes
|
25 Eyes
n=23 Eyes
|
49 Eyes
n=50 Eyes
|
|
Change in visual acuity letter score from enrollment to randomization
|
3 units on a scale
STANDARD_DEVIATION 7 • n=14 Eyes
|
3 units on a scale
STANDARD_DEVIATION 6 • n=23 Eyes
|
3 units on a scale
STANDARD_DEVIATION 7 • n=50 Eyes
|
PRIMARY outcome
Timeframe: 24 weeks after randomizationAt 24 weeks after randomization, mean change in visual acuity letter score, adjusted for visual acuity at time of randomization
Outcome measures
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=63 Eyes
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
|---|---|---|
|
Mean Change in Visual Acuity Letter Score
|
2.7 Letter Score
Standard Deviation 9.8
|
3.0 Letter Score
Standard Deviation 7.1
|
SECONDARY outcome
Timeframe: 24 weeks weeks after randomizationETDRS (Early Treatment Diabetic Retinopathy Study)
Outcome measures
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=63 Eyes
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
|---|---|---|
|
At 24 Weeks After Randomization, Number of Eyes With at Least 10 and at Least 15 Letter Gain (Increase) or Loss (Decrease) in E-ETDRS Letter Score Visual Acuity.
>= 15 Letter Improvement
|
7 Eyes
|
1 Eyes
|
|
At 24 Weeks After Randomization, Number of Eyes With at Least 10 and at Least 15 Letter Gain (Increase) or Loss (Decrease) in E-ETDRS Letter Score Visual Acuity.
>= 10 Letter Improvement
|
14 Eyes
|
9 Eyes
|
|
At 24 Weeks After Randomization, Number of Eyes With at Least 10 and at Least 15 Letter Gain (Increase) or Loss (Decrease) in E-ETDRS Letter Score Visual Acuity.
>= 10 Letter Worsening
|
8 Eyes
|
4 Eyes
|
|
At 24 Weeks After Randomization, Number of Eyes With at Least 10 and at Least 15 Letter Gain (Increase) or Loss (Decrease) in E-ETDRS Letter Score Visual Acuity.
>= 15 Letter Worsening
|
4 Eyes
|
3 Eyes
|
SECONDARY outcome
Timeframe: 24 weeks after randomizationOnly included participants who completed the 24-week visit. Time points for which data were collected for this analysis include 0, 4 8,12, 16, 20, and 24 weeks post randomization.
Outcome measures
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=63 Eyes
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
|---|---|---|
|
Visual Acuity Area Under the Curve (AUC) Between Randomization and 24 Weeks
|
1.9 Letter Score
Standard Deviation 6.3
|
2.5 Letter Score
Standard Deviation 4.4
|
SECONDARY outcome
Timeframe: 24 weeks after randomizationChange in optical coherence tomography (OCT) central subfield thickness (in microns) was truncated to 3 standard deviations from the mean \[-372, +201\] (calculated using observed changes at 24 weeks combining all treatment groups), to minimize the effect of outliers. Two values were truncated in the sham + ranibizumab group: one on the negative end, and one on the positive end.
Outcome measures
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=63 Eyes
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
|---|---|---|
|
Mean Change in OCT CSF Thickness, Adjusted for Thickness at Time of Randomization
|
-110 microns
Standard Deviation 86
|
-62 microns
Standard Deviation 97
|
SECONDARY outcome
Timeframe: 24 weeks after randomizationChange in optical coherence tomography (OCT) central subfield (CSF) thickness (in microns) was truncated to 3 standard deviations from the mean \[-372, +201\] (calculated using observed changes at 24 weeks combining all treatment groups), to minimize the effect of outliers. Two values were truncated in the sham + ranibizumab group: one on the negative end, and one on the positive end.
Outcome measures
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=63 Eyes
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
|---|---|---|
|
Number of Eyes With ≥1 and ≥2 logOCT Step Gain or Loss in CSF Thickness
>=1 LogOCT step improvement
|
34 Eyes
|
22 Eyes
|
|
Number of Eyes With ≥1 and ≥2 logOCT Step Gain or Loss in CSF Thickness
>= 2 LogOCT step improvement
|
14 Eyes
|
8 Eyes
|
|
Number of Eyes With ≥1 and ≥2 logOCT Step Gain or Loss in CSF Thickness
>=1 LogOCT step worsening
|
0 Eyes
|
1 Eyes
|
|
Number of Eyes With ≥1 and ≥2 logOCT Step Gain or Loss in CSF Thickness
>=2 LogOCT step worsening
|
0 Eyes
|
1 Eyes
|
SECONDARY outcome
Timeframe: 24 weeks after randomizationGender and OCT machine-specific values for OCT central subfield thickness (in microns) are defined as: \<290 in women and \<305 in men in Zeiss Cirrus; \<305 in women and \<320 in men in Heidelberg Spectralis
Outcome measures
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=63 Eyes
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
|---|---|---|
|
Eyes With OCT CSF Thickness < the Gender-specific Spectral Domain OCT Equivalent of 250 Microns on Zeiss Stratus
|
32 Eyes
|
20 Eyes
|
SECONDARY outcome
Timeframe: 24 weeks after randomizationIncluding participants who completed the 24-week visit. Time points for which data were collected for this analysis include 0, 4 8,12, 16, 20, and 24 weeks post randomization.
Outcome measures
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=63 Eyes
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=64 Eyes
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
|---|---|---|
|
OCT CSF Thickness Area Under the Curve Between Randomization and 24 Weeks
|
-86.9 microns
Standard Deviation 65.6
|
-33.5 microns
Standard Deviation 56.8
|
Adverse Events
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
Serious events: 7 serious events
Other events: 38 other events
Deaths: 0 deaths
Sham + Intravitreal Ranibizumab 0.3 mg
Serious events: 7 serious events
Other events: 29 other events
Deaths: 0 deaths
Bilateral
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=52 participants at risk
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=52 participants at risk；n=51 participants at risk
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
Bilateral
n=13 participants at risk
Participants with one eye enrolled in each arm of the study. A participant could only have one eye in each arm/group, therefore participants in the bilateral group received Intravitreal dexamethasone+intravitreal ranibizumab 0.3mg in one eye and Sham + intravitreal ranibizumab 0.3 mg in the other eye.
|
|---|---|---|---|
|
Cardiac disorders
Diastolic dysfunction
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Endocrine disorders
Hypoglycaemia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Cataract subcapsular
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Retinal detachment
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Infections and infestations
Infection
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Multiple fractures
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Renal and urinary disorders
Acute kidney injury
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 2 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Surgical and medical procedures
Stent placement
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Surgical and medical procedures
Vascular graft
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Vascular disorders
Cerebrovascular accident
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Vascular disorders
Hypertension
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
Other adverse events
| Measure |
Intravitreal Dexamethasone+Intravitreal Ranibizumab 0.3mg
n=52 participants at risk
The initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first. Intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
dexamethasone intravitreal implant: The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ran
|
Sham + Intravitreal Ranibizumab 0.3 mg
n=52 participants at risk；n=51 participants at risk
Intravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
intravitreal ranibizumab 0.3 mg: Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Sham injection: No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.
|
Bilateral
n=13 participants at risk
Participants with one eye enrolled in each arm of the study. A participant could only have one eye in each arm/group, therefore participants in the bilateral group received Intravitreal dexamethasone+intravitreal ranibizumab 0.3mg in one eye and Sham + intravitreal ranibizumab 0.3 mg in the other eye.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Cardiac disorders
Atrial fibrillation
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Endocrine disorders
Diabetes mellitus inadequate control
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Endocrine disorders
Hypoglycaemia
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Asthenopia
|
1.9%
1/52 • Number of events 3 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Blepharitis
|
3.8%
2/52 • Number of events 3 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Cataract
|
5.8%
3/52 • Number of events 3 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Cataract cortical
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Cataract nuclear
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
15.4%
2/13 • Number of events 2 • From Randomization to 24-weeks
|
|
Eye disorders
Cataract subcapsular
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
15.4%
2/13 • Number of events 3 • From Randomization to 24-weeks
|
|
Eye disorders
Conjunctival haemorrhage
|
7.7%
4/52 • Number of events 4 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Corneal defect
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Corneal oedema
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Diabetic retinopathy
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Diplopia
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Dry eye
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 2 • From Randomization to 24-weeks
|
|
Eye disorders
Ectropion
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Eye irritation
|
3.8%
2/52 • Number of events 2 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Eye pain
|
3.8%
2/52 • Number of events 2 • From Randomization to 24-weeks
|
5.9%
3/51 • Number of events 3 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Eye pruritus
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Eyelid ptosis
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Foreign body sensation in eyes
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Iritis
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Metamorphopsia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Ocular discomfort
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Photophobia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Photopsia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Retinal exudates
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Vision blurred
|
13.5%
7/52 • Number of events 7 • From Randomization to 24-weeks
|
7.8%
4/51 • Number of events 5 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/52 • From Randomization to 24-weeks
|
3.9%
2/51 • Number of events 3 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Visual field defect
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Visual impairment
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 2 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Eye disorders
Vitreous adhesions
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Vitreous floaters
|
15.4%
8/52 • Number of events 8 • From Randomization to 24-weeks
|
5.9%
3/51 • Number of events 3 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Eye disorders
Vitreous haemorrhage
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Food poisoning
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Gastritis
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Gastroenteritis viral
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Nausea
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Tooth infection
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Gastrointestinal disorders
Vomiting
|
1.9%
1/52 • Number of events 2 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
General disorders
Pain
|
0.00%
0/52 • From Randomization to 24-weeks
|
3.9%
2/51 • Number of events 2 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
General disorders
Pyrexia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Infections and infestations
Infection
|
0.00%
0/52 • From Randomization to 24-weeks
|
3.9%
2/51 • Number of events 2 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Infections and infestations
Influenza
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Infections and infestations
Onychomycosis
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Infections and infestations
Staphylococcal infection
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Infections and infestations
Viral infection
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Injury, poisoning and procedural complications
Fall
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Injury, poisoning and procedural complications
Head injury
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Injury, poisoning and procedural complications
Wound
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Investigations
Blood calcium decreased
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Investigations
Cardiac murmur
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Investigations
Intraocular pressure increased
|
21.2%
11/52 • Number of events 12 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
23.1%
3/13 • Number of events 3 • From Randomization to 24-weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.9%
1/52 • Number of events 2 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Foot fracture
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Gout
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Multiple fractures
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Polymyalgia rheumatica
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Rib fracture
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Nervous system disorders
Carotid artery occlusion
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Nervous system disorders
Dizziness
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Nervous system disorders
Myasthenia gravis
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Psychiatric disorders
Depression
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Renal and urinary disorders
Urinary tract infection
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
15.4%
2/13 • Number of events 2 • From Randomization to 24-weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
3.9%
2/51 • Number of events 2 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis streptococcal
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 2 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Skin and subcutaneous tissue disorders
Basal cell carcinoma
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Skin and subcutaneous tissue disorders
Skin cancer
|
0.00%
0/52 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
7.7%
1/13 • Number of events 1 • From Randomization to 24-weeks
|
|
Skin and subcutaneous tissue disorders
Skin infection
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Surgical and medical procedures
Knee operation
|
0.00%
0/52 • From Randomization to 24-weeks
|
2.0%
1/51 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Surgical and medical procedures
Tooth extraction
|
3.8%
2/52 • Number of events 3 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
|
Vascular disorders
Hypertension
|
1.9%
1/52 • Number of events 1 • From Randomization to 24-weeks
|
0.00%
0/51 • From Randomization to 24-weeks
|
0.00%
0/13 • From Randomization to 24-weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Trial results can not be discussed until they have been made available to the public
- Publication restrictions are in place
Restriction type: OTHER