A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes Mellitus (RISE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00473330
First received: May 13, 2007
Last updated: July 31, 2013
Last verified: July 2013
Results First Received: December 10, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Diabetes Mellitus
Macular Edema
Interventions: Drug: Ranibizumab
Drug: Sham injection

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were recruited from study sites in the United States and Argentina. There were 10 patients from Argentina.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Ranibizumab 0.3 mg Patients received ranibizumab 0.3 mg monthly administered intravitreally for 36 months.
Ranibizumab 0.5 mg Patients received ranibizumab 0.5 mg monthly administered intravitreally for 36 months.
Sham Injection/Ranibizumab 0.5 mg Patients received a sham intravitreal injection monthly for 24 months. Patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months.

Participant Flow:   Overall Study
    Ranibizumab 0.3 mg     Ranibizumab 0.5 mg     Sham Injection/Ranibizumab 0.5 mg  
STARTED     125     125     127  
COMPLETED     98     100     86  
NOT COMPLETED     27     25     41  
Adverse Event                 4                 4                 1  
Death                 6                 4                 4  
Lost to Follow-up                 5                 5                 10  
Physician Decision                 2                 1                 3  
Subject non-compliance                 1                 2                 1  
Subject needed other treatment                 0                 1                 3  
Subject's decision                 9                 8                 19  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Ranibizumab 0.3 mg Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 24 months.
Ranibizumab 0.5 mg Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 24 months.
Sham Injection Patients randomized to this group received a sham intravitreal injection monthly for 24 months.
Total Total of all reporting groups

Baseline Measures
    Ranibizumab 0.3 mg     Ranibizumab 0.5 mg     Sham Injection     Total  
Number of Participants  
[units: participants]
  125     125     127     377  
Age  
[units: years]
Mean ± Standard Deviation
  61.7  ± 8.9     62.8  ± 10.0     61.8  ± 9.8     62.1  ± 9.6  
Gender  
[units: participants]
       
Female     52     60     53     165  
Male     73     65     74     212  



  Outcome Measures
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1.  Primary:   Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24   [ Time Frame: Baseline to Month 24 ]

2.  Secondary:   Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36   [ Time Frame: Baseline to Months 24 and 36 ]

3.  Secondary:   Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24 and 36   [ Time Frame: Months 24 and 36 ]

4.  Secondary:   Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24 and 36   [ Time Frame: Baseline to Months 24 and 36 ]

5.  Secondary:   Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline   [ Time Frame: Baseline to Months 24 and 36 ]

6.  Secondary:   Mean Change From Baseline in Central Foveal Thickness at Months 24 and 36   [ Time Frame: Baseline to Months 24 and 36 ]

7.  Secondary:   Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and 36   [ Time Frame: Baseline to Months 24 and 36 ]

8.  Secondary:   Percentage of Patients With Resolution of Leakage at Month 24   [ Time Frame: Baseline to Month 24 ]

9.  Secondary:   Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36   [ Time Frame: Baseline to Months 24 and 36 ]

10.  Secondary:   Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 36   [ Time Frame: Baseline to Month 36 ]


  Serious Adverse Events
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Time Frame Adverse events were recorded from the first day of treatment through Month 36.
Additional Description The sham Months 0-36 group includes patients randomized to sham; the majority crossed-over to ranibizumab 0.5 mg in Year 3. The sham Months 0-24 group includes patients who received sham during the first 24 months of the study. Serious adverse events that occurred after early crossover to ranibizumab (defined as prior to Month 25) are not included.

Reporting Groups
  Description
Ranibizumab 0.3 mg Patients received ranibizumab 0.3 mg monthly administered intravitreally for 36 months.
Ranibizumab 0.5 mg Patients received ranibizumab 0.5 mg monthly administered intravitreally for 36 months.
Sham Injection/Ranibizumab 0.5 mg - Months 0-36 Patients received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Data in this column represent the safety data in the sham group during the entire 36 months of the trial; most patients crossed over to receive ranibizumab 0.5 mg monthly in the third year.
Sham Injection - Months 0-24 Patients received a sham intravitreal injection monthly for 24 months. Data in this column represent the safety data in the sham group during the first 24 months of the trial when patients were receiving only sham injections. Safety data shown here are also included in the Sham/Ranibizumab 0.5 mg - Months 0-36 column.

Serious Adverse Events
    Ranibizumab 0.3 mg     Ranibizumab 0.5 mg     Sham Injection/Ranibizumab 0.5 mg - Months 0-36     Sham Injection - Months 0-24  
Total, serious adverse events          
# participants affected / at risk     60/125 (48.00%)     69/125 (55.20%)     59/124 (47.58%)     46/123 (37.40%)  
Blood and lymphatic system disorders          
Anaemia † 1        
# participants affected / at risk     1/125 (0.80%)     5/125 (4.00%)     1/124 (0.81%)     1/123 (0.81%)  
Haemorrhagic anaemia † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Leukocytosis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Cardiac disorders          
Acute myocardial infarction † 1        
# participants affected / at risk     1/125 (0.80%)     4/125 (3.20%)     0/124 (0.00%)     0/123 (0.00%)  
Angina pectoris † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     3/124 (2.42%)     1/123 (0.81%)  
Angina unstable † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Arrhythmia † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Atrial fibrillation † 1        
# participants affected / at risk     3/125 (2.40%)     2/125 (1.60%)     2/124 (1.61%)     2/123 (1.63%)  
Atrial flutter † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Atrioventricular block complete † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Bradycardia † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     1/124 (0.81%)     1/123 (0.81%)  
Cardiac arrest † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     1/124 (0.81%)     1/123 (0.81%)  
Cardiac failure acute † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Cardiac failure congestive † 1        
# participants affected / at risk     7/125 (5.60%)     7/125 (5.60%)     4/124 (3.23%)     2/123 (1.63%)  
Congestive cardiomyopathy † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Coronary artery disease † 1        
# participants affected / at risk     6/125 (4.80%)     3/125 (2.40%)     2/124 (1.61%)     1/123 (0.81%)  
Coronary artery occlusion † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Heart valve incompetence † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Ischaemic cardiomyopathy † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Myocardial infarction † 1        
# participants affected / at risk     6/125 (4.80%)     1/125 (0.80%)     3/124 (2.42%)     3/123 (2.44%)  
Ventricular fibrillation † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Ventricular tachycardia † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Ear and labyrinth disorders          
Vertigo † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Eye disorders          
Cataract (F) † 1 [3]        
# participants affected / at risk     3/125 (2.40%)     1/125 (0.80%)     3/124 (2.42%)     1/123 (0.81%)  
Cataract (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Choroidal neovascularisation (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Corneal degeneration (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Cystoid macular oedema (F) † 1 [3]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Diabetic retinal oedema (F) † 1 [3]        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Diabetic retinal oedema (S) † 1 [4]        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Glaucoma (F) † 1 [3]        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Iritis (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Macular oedema (F) † 1 [3]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Macular oedema (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     2/123 (1.63%)  
Optic ischaemic neuropathy (F) † 1 [3]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Posterior capsule opacification (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Retinal detachment (F) † 1 [3]        
# participants affected / at risk     2/125 (1.60%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Retinal detachment (S) † 1 [5]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     2/124 (1.61%)     1/123 (0.81%)  
Retinal haemorrhage (F) † 1 [3]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Retinal haemorrhage (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Retinal neovascularisation (F) † 1 [3]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Retinal tear (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Visual acuity reduced (F) † 1 [3]        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     3/124 (2.42%)     0/123 (0.00%)  
Visual acuity reduced (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     1/124 (0.81%)     2/123 (1.63%)  
Vitreous detachment (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Vitreous haemorrhage (F) † 1 [3]        
# participants affected / at risk     4/125 (3.20%)     3/125 (2.40%)     3/124 (2.42%)     2/123 (1.63%)  
Vitreous haemorrhage (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     3/125 (2.40%)     5/124 (4.03%)     4/123 (3.25%)  
Gastrointestinal disorders          
Abdominal pain † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Abdominal pain upper † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Ascites † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Colitis ischaemic † 1        
# participants affected / at risk     2/125 (1.60%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Colitis ulcerative † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Colonic polyp † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Constipation † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Duodenal ulcer haemorrhage † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Erosive oesophagitis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Gastric ulcer † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Gastritis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Gastrointestinal haemorrhage † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     1/124 (0.81%)     0/123 (0.00%)  
Haematemesis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Impaired gastric emptying † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Large intestine perforation † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Lower gastrointestinal haemorrhage † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Pancreatitis † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Pancreatitis acute † 1        
# participants affected / at risk     0/125 (0.00%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Rectal haemorrhage † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Retroperitoneal haemorrhage † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Small intestinal obstruction † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     1/124 (0.81%)     1/123 (0.81%)  
General disorders          
Chest pain † 1        
# participants affected / at risk     2/125 (1.60%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Death † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
General physical health deterioration † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Oedema peripheral † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Pyrexia † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Hepatobiliary disorders          
Cholecystitis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     2/124 (1.61%)     1/123 (0.81%)  
Cholecystitis acute † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Cholecystitis chronic † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Cholelithiasis † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Hepatic cirrhosis † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Infections and infestations          
Abscess limb † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Abscess oral † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Acute sinusitis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Bronchitis † 1        
# participants affected / at risk     2/125 (1.60%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Bronchopneumonia † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Cardiac infection † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Cellulitis † 1        
# participants affected / at risk     2/125 (1.60%)     4/125 (3.20%)     1/124 (0.81%)     1/123 (0.81%)  
Cholecystitis infective † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Clostridial infection † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Clostridium difficile colitis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Device related infection † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Device related sepsis † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Diabetic foot infection † 1        
# participants affected / at risk     0/125 (0.00%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Empyema † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Endophthalmitis (F) † 1 [3]        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Endophthalmitis (S) † 1 [4]        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Gangrene † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Gas gangrene † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Gastroenteritis † 1        
# participants affected / at risk     0/125 (0.00%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Gastroenteritis viral † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Gastrointestinal infection † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Helicobacter gastritis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Herpes zoster † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Infectious peritonitis † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Keratitis bacterial (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Lobar pneumonia † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Localised infection † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     2/124 (1.61%)     2/123 (1.63%)  
Osteomyelitis † 1        
# participants affected / at risk     2/125 (1.60%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Pelvic abscess † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Pneumonia † 1        
# participants affected / at risk     6/125 (4.80%)     5/125 (4.00%)     3/124 (2.42%)     3/123 (2.44%)  
Pneumonia staphylococcal † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Sepsis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Septic shock † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Staphylococcal infection † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Urinary tract infection bacterial † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Injury, poisoning and procedural complications          
Ankle fracture † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Arteriovenous fistula site haematoma † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Cataract traumatic (S) † 1 [4]        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Comminuted fracture † 1        
# participants affected / at risk     2/125 (1.60%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Drug toxicity † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     0/124 (0.00%)     1/123 (0.81%)  
Fall † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Femoral neck fracture † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Femur fracture † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Foreign body † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Hip fracture † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Limb crushing injury † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Limb injury † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Medication error (S) † 1 [4]        
# participants affected / at risk     1/125 (0.80%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Overdose † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Postoperative ileus † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Road traffic accident † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Toxicity to various agents † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Upper limb fracture † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Investigations          
Blood glucose increased † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Blood potassium increased † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Full blood count decreased † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Intraocular pressure increased (S) † 1 [4]        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Troponin increased † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Metabolism and nutrition disorders          
Dehydration † 1        
# participants affected / at risk     1/125 (0.80%)     2/125 (1.60%)     2/124 (1.61%)     1/123 (0.81%)  
Diabetes mellitus † 1        
# participants affected / at risk     2/125 (1.60%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Diabetes mellitus inadequate control † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Diabetic ketoacidosis † 1        
# participants affected / at risk     0/125 (0.00%)     2/125 (1.60%)     1/124 (0.81%)     1/123 (0.81%)  
Hyperglycaemia † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Hypoglycaemia † 1        
# participants affected / at risk     1/125 (0.80%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Hyponatraemia † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Musculoskeletal and connective tissue disorders          
Arthritis † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Back pain † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Cervical spinal stenosis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Costochondritis † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Muscle spasms † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Muscular weakness † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Rhabdomyolysis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Rheumatoid arthritis † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Adenocarcinoma † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Basal cell carcinoma † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Breast cancer † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Breast cancer metastatic † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Colon cancer † 1        
# participants affected / at risk     0/125 (0.00%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Gastrointestinal neoplasm † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Hepatic neoplasm malignant † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Lung neoplasm malignant † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Melanoma recurrent † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Prostate cancer † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     1/124 (0.81%)     1/123 (0.81%)  
Rectal cancer † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Thyroid cancer † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Nervous system disorders          
Cerebrovascular accident † 1        
# participants affected / at risk     1/125 (0.80%)     5/125 (4.00%)     1/124 (0.81%)     1/123 (0.81%)  
Convulsion † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Diabetic hyperosmolar coma † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Dizziness † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     1/123 (0.81%)  
Hypoaesthesia † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Ischaemic stroke † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     2/124 (1.61%)     1/123 (0.81%)  
Lacunar infarction † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Metabolic encephalopathy † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Presyncope † 1        
# participants affected / at risk     0/125 (0.00%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Syncope † 1        
# participants affected / at risk     2/125 (1.60%)     3/125 (2.40%)     1/124 (0.81%)     1/123 (0.81%)  
Transient ischaemic attack † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     3/124 (2.42%)     3/123 (2.44%)  
Psychiatric disorders          
Anxiety † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Confusional state † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Delusion † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Depression † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Schizophrenia † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Renal and urinary disorders          
Diabetic nephropathy † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Haematuria † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Nephrolithiasis † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Nephrotic syndrome † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Renal artery arteriosclerosis † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Renal failure † 1        
# participants affected / at risk     4/125 (3.20%)     2/125 (1.60%)     3/124 (2.42%)     1/123 (0.81%)  
Renal failure acute † 1        
# participants affected / at risk     3/125 (2.40%)     0/125 (0.00%)     2/124 (1.61%)     2/123 (1.63%)  
Renal failure chronic † 1        
# participants affected / at risk     4/125 (3.20%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Stress urinary incontinence † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Reproductive system and breast disorders          
Benign prostatic hyperplasia † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Endometrial hyperplasia † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Respiratory, thoracic and mediastinal disorders          
Acute pulmonary oedema † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Asthma † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Chronic obstructive pulmonary disease † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     2/124 (1.61%)     1/123 (0.81%)  
Hypoxia † 1        
# participants affected / at risk     1/125 (0.80%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Pleural effusion † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Pulmonary embolism † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Pulmonary oedema † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     1/124 (0.81%)     1/123 (0.81%)  
Pulmonary thrombosis † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Respiratory distress † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Respiratory failure † 1        
# participants affected / at risk     2/125 (1.60%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Skin and subcutaneous tissue disorders          
Skin ulcer † 1        
# participants affected / at risk     3/125 (2.40%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Surgical and medical procedures          
Toe amputation † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Vascular disorders          
Accelerated hypertension † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Aortic stenosis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Arterial occlusive disease † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Arteriosclerosis † 1        
# participants affected / at risk     2/125 (1.60%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Deep vein thrombosis † 1        
# participants affected / at risk     0/125 (0.00%)     2/125 (1.60%)     0/124 (0.00%)     0/123 (0.00%)  
Femoral artery occlusion † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Hypertension † 1        
# participants affected / at risk     2/125 (1.60%)     5/125 (4.00%)     0/124 (0.00%)     1/123 (0.81%)  
Hypertensive emergency † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Hypotension † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     1/124 (0.81%)     0/123 (0.00%)  
Intermittent claudication † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Orthostatic hypotension † 1        
# participants affected / at risk     1/125 (0.80%)     0/125 (0.00%)     0/124 (0.00%)     0/123 (0.00%)  
Peripheral arterial occlusive disease † 1        
# participants affected / at risk     0/125 (0.00%)     0/125 (0.00%)     1/124 (0.81%)     1/123 (0.81%)  
Thrombosis † 1        
# participants affected / at risk     0/125 (0.00%)     1/125 (0.80%)     0/124 (0.00%)     0/123 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (13.1)
[3] (F)=fellow eye
[4] (S)=study eye
[5] (S)-study eye




  Other Adverse Events


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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:  
Name/Title: Medical Communications
Organization: Genentech, Inc.
phone: 800 821-8590


No publications provided by Genentech

Publications automatically indexed to this study:

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT00473330     History of Changes
Other Study ID Numbers: FVF4170g
Study First Received: May 13, 2007
Results First Received: December 10, 2012
Last Updated: July 31, 2013
Health Authority: United States: Food and Drug Administration