Trial Outcomes & Findings for Systemic Vascular Endothelial Growth Factor (VEGF) Protein Dynamics Following Intravitreal Injections of Ranibizumab Versus Aflibercept in Patients With Neovascular Age-related Macular Degeneration (NCT NCT02257632)
NCT ID: NCT02257632
Last Updated: 2019-05-07
Results Overview
The AUC was calculated using the trapezoidal rule, where all available measurement between Day 1 and Week 12 were used. The AUC was standardized by dividing the calculated value by the number of days from first to last measurement.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
41 participants
Primary outcome timeframe
Baseline up to Week 12 visit (Days 1, 2, 8, 15, 29, 43, 57, 71, 85)
Results posted on
2019-05-07
Participant Flow
The study included adult patients with active, newly diagnosed, and untreated wAMD. A total of 40 patients were treated at 6 study sites across Germany. Patients were treated in an outpatient setting.
At Screening, the eligibility criteria were performed. .
Participant milestones
| Measure |
Ranibizumab
6 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab
3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
22
|
|
Overall Study
Full Analysis Set (FAS)
|
19
|
21
|
|
Overall Study
Safety Set (SAF)
|
19
|
21
|
|
Overall Study
Per-Protocol Set (PPS)
|
17
|
20
|
|
Overall Study
COMPLETED
|
18
|
19
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
Ranibizumab
6 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab
3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
2
|
Baseline Characteristics
Full Analysis Set (FAS)
Baseline characteristics by cohort
| Measure |
Ranibizumab
n=19 Participants
6 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab
n=21 Participants
3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.3 Years
STANDARD_DEVIATION 5.50 • n=5 Participants
|
75.4 Years
STANDARD_DEVIATION 8.94 • n=7 Participants
|
74.9 Years
STANDARD_DEVIATION 7.43 • n=5 Participants
|
|
Sex/Gender, Customized
Female
|
11 Participants
n=5 Participants • Full Analysis Set (FAS)
|
10 Participants
n=7 Participants • Full Analysis Set (FAS)
|
21 Participants
n=5 Participants • Full Analysis Set (FAS)
|
|
Sex/Gender, Customized
Male
|
8 Participants
n=5 Participants • Full Analysis Set (FAS)
|
11 Participants
n=7 Participants • Full Analysis Set (FAS)
|
19 Participants
n=5 Participants • Full Analysis Set (FAS)
|
|
Race/Ethnicity, Customized
Caucasian
|
19 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 12 visit (Days 1, 2, 8, 15, 29, 43, 57, 71, 85)Population: Per-Protocol Set (PPS)
The AUC was calculated using the trapezoidal rule, where all available measurement between Day 1 and Week 12 were used. The AUC was standardized by dividing the calculated value by the number of days from first to last measurement.
Outcome measures
| Measure |
Ranibizumab
n=17 Participants
6 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab
n=20 Participants
3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab
|
|---|---|---|
|
Standardized Area Under the Curve (AUC) for VEGF A Levels by SIMOA (Quanterix's Single Molecule Array) Method for the Comparative Phase
|
18.78 pg/mL
Standard Deviation 8.460
|
33.95 pg/mL
Standard Deviation 7.659
|
SECONDARY outcome
Timeframe: From study week 12 to 24 (Days 85, 99, 113, 127, 141, 155, 169)Population: Per-Protocol Set (PPS)
Systemic VEGF-A protein levels in patients switching from monthly 2 mg aflibercept injections to monthly 0.5 mg ranibizumab compared to patients treated with monthly 0.5 mg ranibizumab from baseline (standardized area under the curve)
Outcome measures
| Measure |
Ranibizumab
n=17 Participants
6 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab
n=20 Participants
3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab
|
|---|---|---|
|
Systemic VEGF-A Protein Levels From Study Week 12 to 24
|
17.93 pg/mL
Standard Deviation 5.316
|
29.07 pg/mL
Standard Deviation 7.863
|
SECONDARY outcome
Timeframe: From study week 12 to 24Population: Per-Protocol Set (PPS) Number of participants analyzed at each time point represents patients with a value for both baseline and the specific post-baseline visit
Adjustment of systemic VEGF-A levels of patients switching from aflibercept to ranibizumab to levels comparable to baseline or to levels comparable as in patients treated from baseline with ranibizumab
Outcome measures
| Measure |
Ranibizumab
n=17 Participants
6 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab
n=20 Participants
3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab
|
|---|---|---|
|
Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
Change from Baseline at Week 12
|
-1.37 pg/ml
Standard Deviation 5.369
|
23.73 pg/ml
Standard Deviation 13.700
|
|
Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
Change from Baseline at Week 14
|
-1.00 pg/ml
Standard Deviation 6.128
|
21.93 pg/ml
Standard Deviation 15.638
|
|
Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
Change from Baseline at Week 16
|
-0.01 pg/ml
Standard Deviation 4.675
|
19.26 pg/ml
Standard Deviation 16.432
|
|
Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
Change from Baseline at Week 18
|
1.99 pg/ml
Standard Deviation 5.582
|
11.61 pg/ml
Standard Deviation 10.844
|
|
Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
Change from Baseline at Week 20
|
1.62 pg/ml
Standard Deviation 6.460
|
4.84 pg/ml
Standard Deviation 11.065
|
|
Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
Change from Baseline at Week 22
|
0.66 pg/ml
Standard Deviation 8.109
|
2.45 pg/ml
Standard Deviation 8.543
|
|
Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
Change from Baseline at Week 24
|
-1.18 pg/ml
Standard Deviation 3.664
|
0.96 pg/ml
Standard Deviation 9.553
|
Adverse Events
Ranibizumab (Up to Month 3)
Serious events: 3 serious events
Other events: 14 other events
Deaths: 0 deaths
Ranibizumab (After Month 3)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Aflibercept and Ranibizumab (Up to Month 3 - Aflibercept)
Serious events: 1 serious events
Other events: 17 other events
Deaths: 0 deaths
Aflibercept and Ranibizumab (After Month 3 - Ranibizumab)
Serious events: 3 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ranibizumab (Up to Month 3)
n=19 participants at risk
3 monthly intravitreal injections of 0.5 mg ranibizumab
|
Ranibizumab (After Month 3)
n=19 participants at risk
3 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab (Up to Month 3 - Aflibercept)
n=21 participants at risk
3 monthly intravitreal injections of 2 mg aflibercept (AEs reported that started before switching to ranibizumab)
|
Aflibercept and Ranibizumab (After Month 3 - Ranibizumab)
n=21 participants at risk
3 monthly intravitreal injections of 0.5 mg ranibizumab (AEs reported that started on or after switching to ranibizumab)
|
|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Eye disorders
Optic nerve cupping
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Eye disorders
Retinal pigment epithelial tear
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Infections and infestations
Pneumonia
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Bone cyst
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign lung neoplasm
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
Other adverse events
| Measure |
Ranibizumab (Up to Month 3)
n=19 participants at risk
3 monthly intravitreal injections of 0.5 mg ranibizumab
|
Ranibizumab (After Month 3)
n=19 participants at risk
3 monthly intravitreal injections of 0.5 mg ranibizumab
|
Aflibercept and Ranibizumab (Up to Month 3 - Aflibercept)
n=21 participants at risk
3 monthly intravitreal injections of 2 mg aflibercept (AEs reported that started before switching to ranibizumab)
|
Aflibercept and Ranibizumab (After Month 3 - Ranibizumab)
n=21 participants at risk
3 monthly intravitreal injections of 0.5 mg ranibizumab (AEs reported that started on or after switching to ranibizumab)
|
|---|---|---|---|---|
|
Cardiac disorders
Aortic valve disease
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Cardiac disorders
Aortic valve incompetence
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Cardiac disorders
Cardiac discomfort
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Cardiac disorders
Cardiac fibrillation
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Cardiac disorders
Cardiovascular disorder
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Cardiac disorders
Sinus bradycardia
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Cardiac disorders
Tricuspid valve incompetence
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Ear and labyrinth disorders
Vertigo
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Endocrine disorders
Thyroid mass
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Anterior chamber cell
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Eye disorders
Blepharitis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Choroidal neovascularisation
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
|
Eye disorders
Conjunctival erosion
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Conjunctival haemorrhage
|
15.8%
3/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
23.8%
5/21 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
|
Eye disorders
Conjunctival hyperaemia
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Corneal erosion
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Dry eye
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Eye discharge
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Eye pain
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Foreign body sensation in eyes
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Lacrimation increased
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Macular fibrosis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Metamorphopsia
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Ocular discomfort
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Pinguecula
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Retinal fibrosis
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Eye disorders
Retinal scar
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Subretinal fluid
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Vision blurred
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Visual impairment
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Eye disorders
Vitreous detachment
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
|
Eye disorders
Vitreous floaters
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
General disorders
Fibrosis
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
General disorders
Influenza like illness
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
General disorders
Injection site pain
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
General disorders
Sensation of foreign body
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Infections and infestations
Bronchitis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Infections and infestations
Conjunctivitis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Infections and infestations
Hordeolum
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Infections and infestations
Influenza
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Infections and infestations
Rhinitis
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Infections and infestations
Viral upper respiratory tract infection
|
15.8%
3/19 • 28 weeks
|
10.5%
2/19 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
19.0%
4/21 • 28 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Investigations
Blood pressure increased
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Investigations
Body temperature increased
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Investigations
Electrocardiogram abnormal
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Investigations
Haemoglobin E present
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Investigations
Intraocular pressure increased
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
|
Investigations
Mean cell haemoglobin concentration increased
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Investigations
Mean cell haemoglobin increased
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Metabolism and nutrition disorders
Iron deficiency
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.5%
2/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Fibromyalgia
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
5.3%
1/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Nervous system disorders
Headache
|
5.3%
1/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Nervous system disorders
Monoparesis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Nervous system disorders
Sciatica
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Psychiatric disorders
Insomnia
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Renal and urinary disorders
Chronic kidney disease
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial wall thickening
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Melanosis
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
9.5%
2/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Sebaceous gland disorder
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Surgical and medical procedures
Jaw operation
|
0.00%
0/19 • 28 weeks
|
5.3%
1/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
|
Vascular disorders
Hypertension
|
0.00%
0/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
4.8%
1/21 • 28 weeks
|
|
Vascular disorders
Intermittent claudication
|
5.3%
1/19 • 28 weeks
|
0.00%
0/19 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
0.00%
0/21 • 28 weeks
|
Additional Information
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 (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER