Time Frame |
Reporting Group (RG) 1 + 2: Data for Interim Analysis, cut-off Oct 17, 2006; RG 3: Data during and after unblinding (until Nov 21, 2008); RG 4: Data prior to date of unblinding (Feb 9, 2007); RG 5: Data after unblinding (Open Label; until Nov 21, 2008)
|
Adverse Event Reporting Description |
RG 1 + 3 description: All subjects randomized to Sorafenib treatment; RG 2 + 4 description: All subjects randomized to Placebo before unblinding (when they were on Placebo, before they had the opportunity to switch to Sorafenib treatment); RG 5 description: All placebo subjects who switched to Sorafenib treatment after unblinding occurred.
|
|
Arm/Group Title
|
Sorafenib (Nexavar) Arm Double-Blind Phase (Interim Data Only)
|
Placebo Arm Double-Blind Phase (Interim Data Only)
|
Sorafenib (Nexavar) Arm Complete (Incl. Open Label Phase)
|
Placebo Arm, Complete Double-Blind Phase
|
Subjects Switching From Placebo to Sorafenib (Open Label Only)
|
Arm/Group Description |
Reporting Group 1 (RG 1): All parti...
|
Reporting Group 2 (RG 2): All parti...
|
Reporting Group 3 (RG 3): All parti...
|
Reporting Group 4 (RG 4): All parti...
|
Reporting Group 5 (RG 5): Participa...
|
Arm/Group Description |
Reporting Group 1 (RG 1): All participants in Double-Blind phase randomized to Sorafenib treatment (data before Oct 17, 2006); Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg once daily (OD) and 400 mg every other day were permitted for adverse events related to study treatment. Note: Safety Data presented here include participants listed in Arms A1 and A2 of the Participant Flow section.
|
Reporting Group 2 (RG 2): All participants in Double-Blind phase randomized to Sorafenib-matching placebo (data before Oct 17, 2006); Sorafenib-matching placebo tablets were orally administered twice daily (bid).
Note: Safety Data presented here include participants listed in Arms B1 and B2 of the Participant Flow section.
|
Reporting Group 3 (RG 3): All participants that initially were randomized to Sorafenib treatment (data before unblinding (= Double-Blind phase) and after unblinding (= Open Label phase)), until Nov 21, 2008); Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg once daily (OD) and 400 mg every other day were permitted for adverse events related to study treatment. Note: Safety Data presented here include participants listed in Arms A1 and A2 of the Participant Flow section.
|
Reporting Group 4 (RG 4): All participants that initially were randomized to Placebo (data from Placebo patients before unblinding at Feb 09, 2007); Sorafenib-matching placebo tablets were orally administered twice daily (bid).
Note: Safety Data presented here include participants listed in Arms B1 and B2 of the Participant Flow section.
|
Reporting Group 5 (RG 5): Participants initially randomized to Placebo who switched to Sorafenib in Open Label phase (data after unblinding only, from Feb 09, 2007 until Nov 21, 2008); Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid). Note: Safety Data presented here include participants listed in Arm B2 of the Participant Flow section.
|
|
|
Sorafenib (Nexavar) Arm Double-Blind Phase (Interim Data Only)
|
Placebo Arm Double-Blind Phase (Interim Data Only)
|
Sorafenib (Nexavar) Arm Complete (Incl. Open Label Phase)
|
Placebo Arm, Complete Double-Blind Phase
|
Subjects Switching From Placebo to Sorafenib (Open Label Only)
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
--/-- |
--/-- |
--/-- |
--/-- |
--/-- |
|
|
Sorafenib (Nexavar) Arm Double-Blind Phase (Interim Data Only)
|
Placebo Arm Double-Blind Phase (Interim Data Only)
|
Sorafenib (Nexavar) Arm Complete (Incl. Open Label Phase)
|
Placebo Arm, Complete Double-Blind Phase
|
Subjects Switching From Placebo to Sorafenib (Open Label Only)
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
153/297 (51.52%) |
164/302 (54.30%) |
191/297 (64.31%) |
185/302 (61.26%) |
26/47 (55.32%) |
Blood and lymphatic system disorders |
|
|
|
|
|
neutrophils |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
hemoglobin |
8/297 (2.69%) |
6/302 (1.99%) |
11/297 (3.70%) |
7/302 (2.32%) |
0/47 (0.00%) |
leukocytes |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
inr |
1/297 (0.34%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
edema: limb |
2/297 (0.67%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
lymphatics - other |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
lymphedema-related fibrosis |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
edema: head and neck |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
Cardiac disorders |
|
|
|
|
|
supraventricular arrhythmia, atrial fibrillation |
1/297 (0.34%) |
2/302 (0.66%) |
1/297 (0.34%) |
3/302 (0.99%) |
0/47 (0.00%) |
conduction abnormality, av block - first degree |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
supraventricular arrhythmia, sinus tachycardia |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
ventricular arrhythmia, ventricular fibrillation |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
ventricular arrhythmia, ventricular tachycardia |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
left ventricular diastolic dysfunction |
2/297 (0.67%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
hypertension |
1/297 (0.34%) |
1/302 (0.33%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
cardiac ischemia/infarction |
8/297 (2.69%) |
4/302 (1.32%) |
9/297 (3.03%) |
5/302 (1.66%) |
1/47 (2.13%) |
hypotension |
1/297 (0.34%) |
2/302 (0.66%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
cardiac general - other |
0/297 (0.00%) |
3/302 (0.99%) |
0/297 (0.00%) |
3/302 (0.99%) |
0/47 (0.00%) |
right ventricular dysfunction |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
left ventricular systolic dysfunction |
1/297 (0.34%) |
2/302 (0.66%) |
2/297 (0.67%) |
2/302 (0.66%) |
0/47 (0.00%) |
conduction abnormality, asystole |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
conduction abnormality, av block-3rd degree (complete av block |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
cardiac arrhythmia - other |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
cardiopulmonary arrest |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
Endocrine disorders |
|
|
|
|
|
hyperthyroidism |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
adrenal insufficiency |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
Eye disorders |
|
|
|
|
|
retinal detachment |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
Gastrointestinal disorders |
|
|
|
|
|
anorexia |
3/297 (1.01%) |
1/302 (0.33%) |
3/297 (1.01%) |
1/302 (0.33%) |
0/47 (0.00%) |
ascites |
14/297 (4.71%) |
13/302 (4.30%) |
16/297 (5.39%) |
20/302 (6.62%) |
4/47 (8.51%) |
colitis |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
0/302 (0.00%) |
0/47 (0.00%) |
constipation |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
dehydration |
9/297 (3.03%) |
1/302 (0.33%) |
10/297 (3.37%) |
1/302 (0.33%) |
0/47 (0.00%) |
diarrhea |
14/297 (4.71%) |
5/302 (1.66%) |
16/297 (5.39%) |
5/302 (1.66%) |
1/47 (2.13%) |
dysphagia |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
enteritis |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
gastritis |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
nausea |
0/297 (0.00%) |
4/302 (1.32%) |
0/297 (0.00%) |
3/302 (0.99%) |
0/47 (0.00%) |
gi - other |
4/297 (1.35%) |
0/302 (0.00%) |
6/297 (2.02%) |
0/302 (0.00%) |
1/47 (2.13%) |
perforation, gi, colon |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
stricture, gi, biliary tree |
0/297 (0.00%) |
1/302 (0.33%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
ulcer, gi, duodenum |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
1/47 (2.13%) |
ulcer, gi, stomach |
1/297 (0.34%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
vomiting |
5/297 (1.68%) |
4/302 (1.32%) |
5/297 (1.68%) |
4/302 (1.32%) |
0/47 (0.00%) |
cholecystitis |
1/297 (0.34%) |
0/302 (0.00%) |
3/297 (1.01%) |
0/302 (0.00%) |
0/47 (0.00%) |
liver dysfunction |
21/297 (7.07%) |
14/302 (4.64%) |
21/297 (7.07%) |
18/302 (5.96%) |
1/47 (2.13%) |
hepatobiliary - other |
11/297 (3.70%) |
16/302 (5.30%) |
16/297 (5.39%) |
22/302 (7.28%) |
5/47 (10.64%) |
pancreatitis |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
distension |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
obstruction, gi, small bowel nos |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
perforation, gi, appendix |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
1/47 (2.13%) |
General disorders |
|
|
|
|
|
death not associated with ctcae term, death nos |
1/297 (0.34%) |
4/302 (1.32%) |
1/297 (0.34%) |
5/302 (1.66%) |
1/47 (2.13%) |
death not associated with ctcae term, disease progression nos |
56/297 (18.86%) |
61/302 (20.20%) |
68/297 (22.90%) |
66/302 (21.85%) |
10/47 (21.28%) |
death not associated with ctcae term, multi-organ failure |
1/297 (0.34%) |
0/302 (0.00%) |
4/297 (1.35%) |
0/302 (0.00%) |
0/47 (0.00%) |
death not associated with ctcae term, sudden death |
0/297 (0.00%) |
1/302 (0.33%) |
1/297 (0.34%) |
1/302 (0.33%) |
1/47 (2.13%) |
fever |
3/297 (1.01%) |
4/302 (1.32%) |
4/297 (1.35%) |
4/302 (1.32%) |
1/47 (2.13%) |
insomnia |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
0/302 (0.00%) |
0/47 (0.00%) |
fatigue |
5/297 (1.68%) |
9/302 (2.98%) |
7/297 (2.36%) |
6/302 (1.99%) |
1/47 (2.13%) |
weight loss |
0/297 (0.00%) |
3/302 (0.99%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
constitutional symptoms - other |
3/297 (1.01%) |
6/302 (1.99%) |
6/297 (2.02%) |
8/302 (2.65%) |
2/47 (4.26%) |
pain, back |
3/297 (1.01%) |
3/302 (0.99%) |
3/297 (1.01%) |
4/302 (1.32%) |
0/47 (0.00%) |
pain, extremity-limb |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
pain, tumor pain |
1/297 (0.34%) |
1/302 (0.33%) |
2/297 (0.67%) |
1/302 (0.33%) |
0/47 (0.00%) |
pain, abdomen nos |
7/297 (2.36%) |
8/302 (2.65%) |
10/297 (3.37%) |
9/302 (2.98%) |
0/47 (0.00%) |
pain, joint |
3/297 (1.01%) |
0/302 (0.00%) |
3/297 (1.01%) |
1/302 (0.33%) |
0/47 (0.00%) |
pain, bone |
3/297 (1.01%) |
1/302 (0.33%) |
3/297 (1.01%) |
1/302 (0.33%) |
0/47 (0.00%) |
pain, other |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
pain, liver |
0/297 (0.00%) |
2/302 (0.66%) |
0/297 (0.00%) |
3/302 (0.99%) |
0/47 (0.00%) |
pain, neuralgia/peripheral nerve |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
pain, stomach |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
0/302 (0.00%) |
0/47 (0.00%) |
syndromes - other |
2/297 (0.67%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
not coded yet |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
0/302 (0.00%) |
0/47 (0.00%) |
pain, chest/thorax nos |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
tumor flare |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
Infections and infestations |
|
|
|
|
|
infection (documented clinically), abdomen nos |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection (documented clinically), anal/perianal |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection (documented clinically), biliary tree |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection (documented clinically), lung (pneumonia) |
3/297 (1.01%) |
3/302 (0.99%) |
6/297 (2.02%) |
4/302 (1.32%) |
2/47 (4.26%) |
infection (documented clinically), skin (cellulitis) |
1/297 (0.34%) |
1/302 (0.33%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection (documented clinically), soft tissue nos |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection (documented clinically), upper airway nos |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection (documented clinically), urinary tract nos |
3/297 (1.01%) |
0/302 (0.00%) |
3/297 (1.01%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with normal anc, bronchus |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection with normal anc, gallbladder (cholecystitis) |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with normal anc, oral cavity-gums (gingivitis) |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection with normal anc, peritoneal cavity |
0/297 (0.00%) |
2/302 (0.66%) |
0/297 (0.00%) |
2/302 (0.66%) |
0/47 (0.00%) |
infection with normal anc, skin (cellulitis) |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection with normal anc, urinary tract nos |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection - other |
0/297 (0.00%) |
3/302 (0.99%) |
2/297 (0.67%) |
4/302 (1.32%) |
0/47 (0.00%) |
infection with unknown anc, biliary tree |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with unknown anc, lung (pneumonia) |
0/297 (0.00%) |
3/302 (0.99%) |
0/297 (0.00%) |
4/302 (1.32%) |
0/47 (0.00%) |
infection with unknown anc, peritoneal cavity |
1/297 (0.34%) |
2/302 (0.66%) |
1/297 (0.34%) |
2/302 (0.66%) |
0/47 (0.00%) |
infection with unknown anc, urinary tract nos |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
infection with unknown anc, wound |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection (documented clinically), blood |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with normal anc, anal/perianal |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with normal anc, appendix |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with normal anc, pancreas |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with unknown anc, appendix |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
infection with unknown anc, blood |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
1/47 (2.13%) |
infection with unknown anc, bronchus |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
Injury, poisoning and procedural complications |
|
|
|
|
|
intraop injury, biliary tree - common bile duct |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
Metabolism and nutrition disorders |
|
|
|
|
|
ALT |
0/297 (0.00%) |
2/302 (0.66%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
AST |
1/297 (0.34%) |
2/302 (0.66%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
cpk |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
creatinine |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
2/302 (0.66%) |
1/47 (2.13%) |
ggt |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
bilirubin (hyperbilirubinemia) |
6/297 (2.02%) |
4/302 (1.32%) |
6/297 (2.02%) |
5/302 (1.66%) |
1/47 (2.13%) |
hypercalcemia |
2/297 (0.67%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
hyperglycemia |
1/297 (0.34%) |
1/302 (0.33%) |
1/297 (0.34%) |
2/302 (0.66%) |
0/47 (0.00%) |
hyperkalemia |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
hypoalbuminemia |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
hypoglycemia |
5/297 (1.68%) |
3/302 (0.99%) |
5/297 (1.68%) |
3/302 (0.99%) |
1/47 (2.13%) |
hypomagnesemia |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
1/47 (2.13%) |
hyponatremia |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
hypocalcemia |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
1/47 (2.13%) |
hypokalemia |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
1/47 (2.13%) |
Musculoskeletal and connective tissue disorders |
|
|
|
|
|
fracture |
4/297 (1.35%) |
3/302 (0.99%) |
5/297 (1.68%) |
4/302 (1.32%) |
1/47 (2.13%) |
musculoskeletal - other |
2/297 (0.67%) |
3/302 (0.99%) |
3/297 (1.01%) |
3/302 (0.99%) |
0/47 (0.00%) |
device/prosthesis |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
muscle weakness, whole body/generalized |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
Nervous system disorders |
|
|
|
|
|
cns ischemia |
0/297 (0.00%) |
4/302 (1.32%) |
1/297 (0.34%) |
4/302 (1.32%) |
2/47 (4.26%) |
confusion |
1/297 (0.34%) |
1/302 (0.33%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
dizziness |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
encephalopathy |
2/297 (0.67%) |
2/302 (0.66%) |
4/297 (1.35%) |
3/302 (0.99%) |
1/47 (2.13%) |
mood alteration, depression |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
neuropathy: motor |
1/297 (0.34%) |
3/302 (0.99%) |
1/297 (0.34%) |
3/302 (0.99%) |
0/47 (0.00%) |
neurology - other |
0/297 (0.00%) |
3/302 (0.99%) |
0/297 (0.00%) |
3/302 (0.99%) |
0/47 (0.00%) |
neuropathy: sensory |
1/297 (0.34%) |
1/302 (0.33%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
seizure |
1/297 (0.34%) |
2/302 (0.66%) |
1/297 (0.34%) |
2/302 (0.66%) |
0/47 (0.00%) |
somnolence |
2/297 (0.67%) |
2/302 (0.66%) |
2/297 (0.67%) |
2/302 (0.66%) |
0/47 (0.00%) |
syncope (fainting) |
2/297 (0.67%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
cognitive disturbance |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
Renal and urinary disorders |
|
|
|
|
|
renal failure |
1/297 (0.34%) |
8/302 (2.65%) |
2/297 (0.67%) |
8/302 (2.65%) |
1/47 (2.13%) |
obstruction, gu, ureter |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
urinary retention |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
Respiratory, thoracic and mediastinal disorders |
|
|
|
|
|
pleural effusion |
1/297 (0.34%) |
1/302 (0.33%) |
2/297 (0.67%) |
1/302 (0.33%) |
1/47 (2.13%) |
hiccoughs |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
hypoxia |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
pulmonary - other |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
pneumothorax |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
dyspnea (shortness of breath) |
3/297 (1.01%) |
2/302 (0.66%) |
3/297 (1.01%) |
2/302 (0.66%) |
0/47 (0.00%) |
Skin and subcutaneous tissue disorders |
|
|
|
|
|
hand-foot skin reaction |
2/297 (0.67%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
dermatology - other |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
1/47 (2.13%) |
pruritus |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
decubitus |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
1/47 (2.13%) |
wound complication, non-infectious |
0/297 (0.00%) |
0/302 (0.00%) |
2/297 (0.67%) |
0/302 (0.00%) |
0/47 (0.00%) |
rash/desquamation |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
1/47 (2.13%) |
ulceration |
0/297 (0.00%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
1/47 (2.13%) |
Vascular disorders |
|
|
|
|
|
cns hemorrhage |
2/297 (0.67%) |
1/302 (0.33%) |
2/297 (0.67%) |
1/302 (0.33%) |
0/47 (0.00%) |
hematoma |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
hemorrhage, gi, abdomen nos |
2/297 (0.67%) |
3/302 (0.99%) |
2/297 (0.67%) |
3/302 (0.99%) |
0/47 (0.00%) |
hemorrhage, gi, colon |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
hemorrhage, gi, duodenum |
1/297 (0.34%) |
2/302 (0.66%) |
1/297 (0.34%) |
3/302 (0.99%) |
0/47 (0.00%) |
hemorrhage, gi, esophagus |
2/297 (0.67%) |
3/302 (0.99%) |
4/297 (1.35%) |
4/302 (1.32%) |
1/47 (2.13%) |
hemorrhage, gi, varices (esophageal) |
7/297 (2.36%) |
11/302 (3.64%) |
8/297 (2.69%) |
13/302 (4.30%) |
1/47 (2.13%) |
hemorrhage, gi, stomach |
4/297 (1.35%) |
2/302 (0.66%) |
5/297 (1.68%) |
2/302 (0.66%) |
0/47 (0.00%) |
hemorrhage, gi, liver |
4/297 (1.35%) |
1/302 (0.33%) |
6/297 (2.02%) |
1/302 (0.33%) |
0/47 (0.00%) |
hemorrhage, gi, lower gi nos |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
hemorrhage, gi, oral cavity |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
hemorrhage, gi, peritoneal cavity |
0/297 (0.00%) |
6/302 (1.99%) |
2/297 (0.67%) |
8/302 (2.65%) |
0/47 (0.00%) |
hemorrhage, gi, varices (rectal) |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
hemorrhage, gi, upper gi nos |
3/297 (1.01%) |
6/302 (1.99%) |
5/297 (1.68%) |
6/302 (1.99%) |
0/47 (0.00%) |
hemorrhage with surgery |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
hemorrhage - other |
1/297 (0.34%) |
1/302 (0.33%) |
2/297 (0.67%) |
1/302 (0.33%) |
0/47 (0.00%) |
hemorrhage pulmonary, lung |
1/297 (0.34%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
0/47 (0.00%) |
hemorrhage pulmonary, pleura |
0/297 (0.00%) |
1/302 (0.33%) |
0/297 (0.00%) |
1/302 (0.33%) |
0/47 (0.00%) |
peripheral arterial ischemia |
1/297 (0.34%) |
0/302 (0.00%) |
0/297 (0.00%) |
0/302 (0.00%) |
0/47 (0.00%) |
thrombosis/thrombus/embolism |
3/297 (1.01%) |
3/302 (0.99%) |
7/297 (2.36%) |
5/302 (1.66%) |
1/47 (2.13%) |
visceral arterial ischemia |
1/297 (0.34%) |
1/302 (0.33%) |
1/297 (0.34%) |
1/302 (0.33%) |
0/47 (0.00%) |
hemorrhage, gi, rectum |
0/297 (0.00%) |
0/302 (0.00%) |
1/297 (0.34%) |
0/302 (0.00%) |
1/47 (2.13%) |
Indicates events were collected by non-systematic assessment
Term from vocabulary, NCI-CTCAE v. 3.0
|
|
Frequency Threshold for Reporting Other Adverse Events
|
5%
|
|
Sorafenib (Nexavar) Arm Double-Blind Phase (Interim Data Only)
|
Placebo Arm Double-Blind Phase (Interim Data Only)
|
Sorafenib (Nexavar) Arm Complete (Incl. Open Label Phase)
|
Placebo Arm, Complete Double-Blind Phase
|
Subjects Switching From Placebo to Sorafenib (Open Label Only)
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
275/297 (92.59%) |
259/302 (85.76%) |
281/297 (94.61%) |
271/302 (89.74%) |
43/47 (91.49%) |
Blood and lymphatic system disorders |
|
|
|
|
|
hemoglobin |
25/297 (8.42%) |
22/302 (7.28%) |
36/297 (12.12%) |
25/302 (8.28%) |
5/47 (10.64%) |
edema: limb |
45/297 (15.15%) |
53/302 (17.55%) |
59/297 (19.87%) |
57/302 (18.87%) |
9/47 (19.15%) |
platelets |
9/297 (3.03%) |
7/302 (2.32%) |
15/297 (5.05%) |
8/302 (2.65%) |
0/47 (0.00%) |
Cardiac disorders |
|
|
|
|
|
hypertension |
27/297 (9.09%) |
12/302 (3.97%) |
32/297 (10.77%) |
13/302 (4.30%) |
6/47 (12.77%) |
Gastrointestinal disorders |
|
|
|
|
|
anorexia |
83/297 (27.95%) |
52/302 (17.22%) |
89/297 (29.97%) |
56/302 (18.54%) |
8/47 (17.02%) |
ascites |
61/297 (20.54%) |
67/302 (22.19%) |
80/297 (26.94%) |
67/302 (22.19%) |
9/47 (19.15%) |
constipation |
41/297 (13.80%) |
31/302 (10.26%) |
44/297 (14.81%) |
32/302 (10.60%) |
3/47 (6.38%) |
diarrhea |
158/297 (53.20%) |
74/302 (24.50%) |
166/297 (55.89%) |
82/302 (27.15%) |
22/47 (46.81%) |
heartburn |
15/297 (5.05%) |
10/302 (3.31%) |
16/297 (5.39%) |
10/302 (3.31%) |
1/47 (2.13%) |
mucositis (functional/symptomatic), oral cavity |
15/297 (5.05%) |
6/302 (1.99%) |
16/297 (5.39%) |
8/302 (2.65%) |
0/47 (0.00%) |
mucositis (clinical exam), oral cavity |
16/297 (5.39%) |
10/302 (3.31%) |
19/297 (6.40%) |
10/302 (3.31%) |
1/47 (2.13%) |
nausea |
71/297 (23.91%) |
58/302 (19.21%) |
73/297 (24.58%) |
63/302 (20.86%) |
8/47 (17.02%) |
gi - other |
16/297 (5.39%) |
10/302 (3.31%) |
22/297 (7.41%) |
13/302 (4.30%) |
3/47 (6.38%) |
vomiting |
41/297 (13.80%) |
30/302 (9.93%) |
48/297 (16.16%) |
34/302 (11.26%) |
4/47 (8.51%) |
liver dysfunction |
18/297 (6.06%) |
9/302 (2.98%) |
21/297 (7.07%) |
10/302 (3.31%) |
1/47 (2.13%) |
dry mouth |
12/297 (4.04%) |
9/302 (2.98%) |
14/297 (4.71%) |
9/302 (2.98%) |
3/47 (6.38%) |
hemorrhoids |
7/297 (2.36%) |
2/302 (0.66%) |
8/297 (2.69%) |
3/302 (0.99%) |
3/47 (6.38%) |
hepatobiliary - other |
12/297 (4.04%) |
14/302 (4.64%) |
17/297 (5.72%) |
17/302 (5.63%) |
2/47 (4.26%) |
General disorders |
|
|
|
|
|
fever |
29/297 (9.76%) |
28/302 (9.27%) |
35/297 (11.78%) |
30/302 (9.93%) |
2/47 (4.26%) |
insomnia |
21/297 (7.07%) |
22/302 (7.28%) |
26/297 (8.75%) |
23/302 (7.62%) |
5/47 (10.64%) |
fatigue |
133/297 (44.78%) |
132/302 (43.71%) |
145/297 (48.82%) |
144/302 (47.68%) |
23/47 (48.94%) |
weight loss |
89/297 (29.97%) |
28/302 (9.27%) |
93/297 (31.31%) |
31/302 (10.26%) |
10/47 (21.28%) |
pain, back |
36/297 (12.12%) |
38/302 (12.58%) |
47/297 (15.82%) |
42/302 (13.91%) |
4/47 (8.51%) |
pain, abdomen nos |
91/297 (30.64%) |
74/302 (24.50%) |
99/297 (33.33%) |
80/302 (26.49%) |
11/47 (23.40%) |
pain, head/headache |
26/297 (8.75%) |
25/302 (8.28%) |
29/297 (9.76%) |
25/302 (8.28%) |
1/47 (2.13%) |
pain, joint |
20/297 (6.73%) |
26/302 (8.61%) |
20/297 (6.73%) |
27/302 (8.94%) |
1/47 (2.13%) |
pain, stomach |
21/297 (7.07%) |
20/302 (6.62%) |
23/297 (7.74%) |
21/302 (6.95%) |
2/47 (4.26%) |
constitutional symptoms - other |
7/297 (2.36%) |
10/302 (3.31%) |
12/297 (4.04%) |
12/302 (3.97%) |
4/47 (8.51%) |
pain, bone |
12/297 (4.04%) |
13/302 (4.30%) |
16/297 (5.39%) |
15/302 (4.97%) |
0/47 (0.00%) |
pain, liver |
12/297 (4.04%) |
13/302 (4.30%) |
13/297 (4.38%) |
16/302 (5.30%) |
1/47 (2.13%) |
flu-like syndrome |
8/297 (2.69%) |
7/302 (2.32%) |
9/297 (3.03%) |
8/302 (2.65%) |
3/47 (6.38%) |
Infections and infestations |
|
|
|
|
|
infection - other |
6/297 (2.02%) |
3/302 (0.99%) |
16/297 (5.39%) |
6/302 (1.99%) |
8/47 (17.02%) |
Metabolism and nutrition disorders |
|
|
|
|
|
AST |
8/297 (2.69%) |
18/302 (5.96%) |
9/297 (3.03%) |
20/302 (6.62%) |
1/47 (2.13%) |
bilirubin (hyperbilirubinemia) |
24/297 (8.08%) |
23/302 (7.62%) |
28/297 (9.43%) |
26/302 (8.61%) |
1/47 (2.13%) |
Musculoskeletal and connective tissue disorders |
|
|
|
|
|
musculoskeletal - other |
24/297 (8.08%) |
15/302 (4.97%) |
31/297 (10.44%) |
18/302 (5.96%) |
1/47 (2.13%) |
Nervous system disorders |
|
|
|
|
|
mood alteration, depression |
10/297 (3.37%) |
7/302 (2.32%) |
14/297 (4.71%) |
9/302 (2.98%) |
7/47 (14.89%) |
Respiratory, thoracic and mediastinal disorders |
|
|
|
|
|
cough |
24/297 (8.08%) |
16/302 (5.30%) |
26/297 (8.75%) |
18/302 (5.96%) |
3/47 (6.38%) |
dyspnea (shortness of breath) |
26/297 (8.75%) |
22/302 (7.28%) |
33/297 (11.11%) |
24/302 (7.95%) |
3/47 (6.38%) |
voice changes |
27/297 (9.09%) |
4/302 (1.32%) |
27/297 (9.09%) |
5/302 (1.66%) |
1/47 (2.13%) |
Skin and subcutaneous tissue disorders |
|
|
|
|
|
alopecia |
42/297 (14.14%) |
5/302 (1.66%) |
46/297 (15.49%) |
6/302 (1.99%) |
6/47 (12.77%) |
dry skin |
31/297 (10.44%) |
18/302 (5.96%) |
31/297 (10.44%) |
18/302 (5.96%) |
3/47 (6.38%) |
hand-foot skin reaction |
63/297 (21.21%) |
9/302 (2.98%) |
67/297 (22.56%) |
9/302 (2.98%) |
6/47 (12.77%) |
dermatology - other |
26/297 (8.75%) |
12/302 (3.97%) |
30/297 (10.10%) |
15/302 (4.97%) |
5/47 (10.64%) |
pruritus |
40/297 (13.47%) |
33/302 (10.93%) |
44/297 (14.81%) |
35/302 (11.59%) |
5/47 (10.64%) |
rash/desquamation |
55/297 (18.52%) |
42/302 (13.91%) |
59/297 (19.87%) |
46/302 (15.23%) |
6/47 (12.77%) |
erythema multiforme |
1/297 (0.34%) |
3/302 (0.99%) |
1/297 (0.34%) |
4/302 (1.32%) |
3/47 (6.38%) |
Indicates events were collected by non-systematic assessment
Term from vocabulary, NCI-CTCAE v. 3.0
|