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SHARP: A Phase III Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT00105443
Collaborator
(none)
602
Enrollment
178
Locations
2
Arms
44.1
Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is: Find out if patients receiving sorafenib will live longer. Find out if sorafenib has any effect on patient reported outcomes. Find out if sorafenib prevents the growth of or shrinks liver tumors and/or their metastases. Determine the pharmacokinetics (PK) in patients with liver cancer.

Condition or Disease Intervention/Treatment Phase
  • Drug: Sorafenib (Nexavar, BAY43-9006)
  • Drug: Placebo
 Phase 3

Detailed Description

The following abbreviations were used in the Adverse Event section:

  • international normalized ratio (inr)

  • Common Terminology Criteria for Adverse Events (ctcae)

  • Not Otherwise Specified (nos)

  • Gastrointestinal (gi)

  • Central nervous system (cns)

  • Absolute Neutrophil Count (anc)

  • Alanine aminotransferase (ALT)

  • Aspartate aminotransferase (AST)

  • Creatine phosphokinase (cpk)

  • Gammaglutamyltransferase (ggt)

  • Genitourinary (gu)

  • Atrioventricular (av)

Study Design

Study Type:
Interventional
Actual Enrollment :
602 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized, Placebo-controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Study Start Date :
Mar 1, 2005
Actual Primary Completion Date :
Nov 1, 2008
Actual Study Completion Date :
Nov 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sorafenib (Nexavar, BAY43-9006)

Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study.

Drug: Sorafenib (Nexavar, BAY43-9006)
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.
Placebo Comparator: Placebo

Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.

Drug: Placebo
Sorafenib-matching placebo tablets were orally administered twice daily (bid).

Outcome Measures

Primary Outcome Measures

  1. Overall Survival (OS) [from randomization to death due to any cause until an average 7.2 months later up to the data cut-off date approximately 19 months after start of enrollment]

    Overall Survival was defined as the time from date of starting treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

  2. Time to Symptomatic Progression (TTSP) [from randomization to the first documented symptomatic progression until an average 4.8 months later up to the data cut-off date approximately 19 months after start of enrollment]

    TTSP was defined as the time from randomization to the first documented symptomatic progression.

Secondary Outcome Measures

  1. Time to Progression (TTP) [from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 19 months after start of enrollment]

    TTP was defined as the time from randomization to disease progression (radiological only). Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.

  2. Disease Control (DC) [time from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment]

    The DC is defined as the number of subjects with a best response rating of complete response (CR), partial response (PR), or stable disease (SD) that is maintained at least 28 days from the first manifestation of that rating. Definitions: CR = disappearance of all clinical and radiological tumor lesions; PR = at least 30% decrease in sum of the longest diameters of tumor lesions; SD = neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.

  3. Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire [from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment]

    PRO is a disease-specific measure, developed as symptom-focused approach in HCC and measured by the response rates for the PWB and FWB subscales of the 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. The FACT-Hep response rate was based on the number of subjects who achieved the 8-point minimally important difference (MID) for this subscale. FACT-Hep total score ranges from 0 to 180, where the highest score represents a maximum achievable quality of life (QoL) value.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Ages eligible for study: 18 years and above, Genders eligible for study: both

  • Patients who have a life expectancy of at least 12 weeks

  • Patients with histologically or cytologically documented Hepatocellular Carcinoma (HCC)

  • Patients must have at least one tumor lesion that meets both of the following criteria: (1) Accurately measured in at least one dimension according to RECIST (Response Evaluation Criteria in Solid Tumors) (2) Not previously treated with local therapy

  • Patients who have an ECOG (Eastern Cooperative Oncology Group) PS (Performance Status) of 0, 1, or 2

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta [Noninvasive papillary carcinoma], Tis [Carcinoma in situ: "flat tumor"] & T1 [Tumor invades subepithelial connective tissue]). Any cancer curatively treated > 3 years prior to entry is permitted

  • Renal failure requiring hemo- or peritoneal dialysis

  • History of cardiac disease

  • Active clinically serious infections

  • Known history of human immunodeficiency virus (HIV) infection

  • Known central nervous system tumors including metastatic brain disease

  • Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry

Contacts and Locations

Locations

Site City State Country Postal Code
1 Phoenix Arizona United States 85054-4502
2 Tucson Arizona United States 85724
3 Los Angeles California United States 90057
4 Los Angeles California United States 90095-7077
5 Orange California United States 92668-3298
6 San Francisco California United States 94121
7 Stanford California United States 94305
8 Farmington Connecticut United States 06030
9 New Haven Connecticut United States 06510-8019
10 Gainesville Florida United States 32610
11 Miami Florida United States 33136
12 Tampa Florida United States 33612
13 Atlanta Georgia United States 30308
14 Atlanta Georgia United States 30322
15 Chicago Illinois United States 60611
16 Chicago Illinois United States 60612
17 Lexington Kentucky United States 40536
18 Ann Arbor Michigan United States 48109-0362
19 Detroit Michigan United States 48202-2689
20 St. Louis Missouri United States 63104
21 Omaha Nebraska United States 68198-2000
22 Manhasset New York United States 11030-3876
23 New York New York United States 10016
24 New York New York United States 10021
25 New York New York United States 10029
26 New York New York United States 10032
27 Canton Ohio United States 44718
28 Portland Oregon United States 97239
29 Philadelphia Pennsylvania United States 19104
30 Philadelphia Pennsylvania United States 19140
31 Pittsburgh Pennsylvania United States 15213
32 Houston Texas United States 77030-1502
33 Richmond Virginia United States 23249
34 Seattle Washington United States 98104
35 Seattle Washington United States 98195-6174
36 Mar del Plata Buenos Aires Argentina 7600
37 Pilar Buenos Aires Argentina B1629AHJ
38 Bueno Aires Ciudad Auton. de Buenos Aires Argentina C1417DTB
39 Buenos Aires Ciudad Auton. de Buenos Aires Argentina C1120AAF
40 Buenos Aires Ciudad Auton. de Buenos Aires Argentina C1145ADP
41 Buenos Aires Ciudad Auton. de Buenos Aires Argentina C1181ACH
42 San Miguel de Tucumán Tucuman Argentina T4000GTB
43 San Miguel de Tucumán Tucuman Argentina T4000HXU
44 Camperdown New South Wales Australia 2050
45 Randwick New South Wales Australia 2031
46 Westmead New South Wales Australia 2145
47 East Bentleigh Victoria Australia 3165
48 Heidelberg Victoria Australia 3084
49 Melbourne Victoria Australia 3052
50 Brugge Belgium 8000
51 Bruxelles - Brussel Belgium 1070
52 Bruxelles - Brussel Belgium 1090
53 Bruxelles - Brussel Belgium 1200
54 Gent Belgium 9000
55 Leuven Belgium 3000
56 Porto Alegre Rio Grande do Sul Brazil 90035-003
57 Porto Alegre Rio Grande do Sul Brazil 90619900
58 Belo Horizonte Brazil 30180090
59 Belo Horizonte Brazil 30380490
60 Sao Paulo Brazil 01246-903
61 Sofia Bulgaria 1233
62 Sofia Bulgaria 1431
63 Sofia Bulgaria 1527
64 Stara Zagora Bulgaria 6000
65 Varna Bulgaria 9010
66 Calgary Alberta Canada T2N 4N1
67 Edmonton Alberta Canada T6G 2C8
68 Vancouver British Columbia Canada V5Z 1H8
69 Winnipeg Manitoba Canada R2H 2A6
70 London Ontario Canada N6A 5A5
71 Ottawa Ontario Canada K1H 1C4
72 Toronto Ontario Canada M5G 2N2
73 Montreal Quebec Canada H3A 1A1
74 Santiago de Chile Santiago Chile 833-0024
75 Santiago de Chile Chile
76 Santiago Región Metropolitana Chile
77 Zagreb Croatia 10000
78 Bondy France 93143
79 Bordeaux France 33000
80 Clichy France 92110
81 Dijon France 21000
82 Lille Cedex France 59020
83 Marseille France 13005
84 Nantes France 44805
85 Paris France 75020
86 Rennes Cedex France 35062
87 Vandoeuvre-les-nancy France 54500
88 Freiburg Baden-Württemberg Germany 79106
89 Tübingen Baden-Württemberg Germany 72076
90 München Bayern Germany 81377
91 München Bayern Germany 81675
92 Regensburg Bayern Germany 93042
93 Frankfurt Hessen Germany 60590
94 Hannover Niedersachsen Germany 30625
95 Bonn Nordrhein-Westfalen Germany 53105
96 Düsseldorf Nordrhein-Westfalen Germany 40225
97 Essen Nordrhein-Westfalen Germany 45122
98 Mainz Rheinland-Pfalz Germany 55131
99 Homburg Saarland Germany 66421
100 Halle Sachsen-Anhalt Germany 06120
101 Magdeburg Sachsen-Anhalt Germany 39120
102 Berlin Germany 12200
103 Hamburg Germany 20246
104 Haidari Attica Greece 12462
105 Athens Greece 115 27
106 Ioannina Greece 45500
107 Thessaloniki Greece 540 07
108 Thessaloniki Greece 54639
109 Thessaloniki Greece 56403
110 Haifa Israel 84801
111 Petach Tikva Israel 49100
112 Tel Aviv Israel 64239
113 Zrifin Israel 70300
114 Rozzano Milano Italy 20089
115 Avellino Italy 83100
116 Bologna Italy 40138
117 Forlì Italy 47100
118 Milano Italy 20122
119 Milano Italy 20133
120 Padova Italy 35128
121 Palermo Italy 90127
122 Pavia Italy 27100
123 Pisa Italy 56126
124 Roma Italy 00144
125 México Distrito Federal Mexico 14080
126 Monterrey Mexico 64000
127 México, D.F. Mexico 06720
128 México, D.F. Mexico 14050
129 Auckland New Zealand 1023
130 Wellington South New Zealand 6001
131 Comas Lima Peru
132 Lima Cercado Peru LIMA 1
133 Lima Peru LIMA 34
134 Gdansk Poland 80-952
135 Poznan Poland 61-878
136 Warszawa Poland 02-507
137 Warszawa Poland 02-781
138 Timisoara Timis Romania 300223
139 Craiova Dolj Romania 200642
140 Iasi Romania 700111
141 Ekaterinburg Russian Federation 620036
142 Ekaterinburg Russian Federation 620102
143 Kazan Russian Federation 420012
144 Kirov Russian Federation 610002
145 Krasnodar Russian Federation 350040
146 Moscow Russian Federation 105 203
147 Moscow Russian Federation 105229
148 Moscow Russian Federation 111 020
149 Moscow Russian Federation 113 811
150 Moscow Russian Federation 115478
151 Moscow Russian Federation 129 010
152 Moscow Russian Federation 129110
153 St. Petersburg Russian Federation 188663
154 St. Petersburg Russian Federation 195 067
155 St. Petersburg Russian Federation 197758
156 Tolgliatti Russian Federation
157 Badalona Barcelona Spain 08916
158 Cruces/Barakaldo Bilbao Spain 48903
159 Alicante Spain 03010
160 Barcelona Spain 08003
161 Barcelona Spain 08035
162 Barcelona Spain 08036
163 Córdoba Spain 14004
164 Madrid Spain 28006
165 Madrid Spain 28034
166 Madrid Spain 28041
167 Pamplona Spain 31008
168 Valencia Spain 46014
169 St. Gallen Sankt Gallen Switzerland 9007
170 Bern Switzerland 3010
171 Genève Switzerland 1211
172 Zürich Switzerland 8091
173 Bristol Avon United Kingdom BS2 8ED
174 Oxford Oxfordshire United Kingdom OX1 2JD
175 Glasgow Stratchclyde United Kingdom G11 6NT
176 London United Kingdom NW3 2QG
177 London United Kingdom SE1 9RT
178 Newcastle-upon-Tyne United Kingdom NE2 4HH

Sponsors and Collaborators

  • Bayer

Investigators

  • Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00105443
Other Study ID Numbers:
  • 100554
  • 2004-001773-26
First Posted:
Mar 15, 2005
Last Update Posted:
Oct 31, 2014
Last Verified:
Oct 1, 2014
Keywords provided by Bayer
Liver Cancer
Cancer
Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Sorafenib

Study Results

Participant Flow

Recruitment Details Subjects with advanced hepatocellular carcinoma (HCC) were enrolled from Mar 10, 2005 to Apr 11, 2006 at 121 study centers in 21 countries around the Globe.
Pre-assignment Detail After a 28 day screening period (902 subjects), 602 were randomized to Sorafenib (400 mg) twice daily (bid), or matching placebo. Majority of screen failures did not meet inclusion criteria. Efficacy population (intent-to-treat, ITT) was all randomized subjects (602), safety population was all subjects receiving at least 1 dose of study drug (599).
Arm/Group Title A1) Sorafenib (Nexavar, BAY43-9006) - no Open Label Phase A2) Sorafenib (Nexavar, BAY43-9006) - With Open Label Phase B1) Placebo - no Open Label Phase B2) Placebo First - Then Open Label Sorafenib Treatment Phase
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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 of participants in the arm presented here are reported in Reporting Groups (RG) RG1 and RG3 in the Safety section. Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study Note: Safety Data of participants in the arm presented here are reported in Reporting Groups (RG) RG1 and RG3 in the Safety section. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Note: Safety Data of participants in the arm presented here are reported in Reporting Groups (RG) RG2 and RG4 in the Safety section. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study. Note: Safety Data of participants in the arm presented here are reported in Reporting Groups (RG) RG2, RG4, and RG5 in the Safety section.
Period Title: Double-Blind Treatment
STARTED 242 57 256 47
Received Treatment 240 57 255 47
COMPLETED 228 57 245 47
NOT COMPLETED 14 0 11 0
Period Title: Double-Blind Treatment
STARTED 228 57 245 47
Follow-up Only (no Open Label Treatment) 228 0 245 0
Open Label Treatment Only (no Follow-up) 0 47 0 36
Follow-up First, Then Open Label 0 10 0 11
COMPLETED 0 0 0 0
NOT COMPLETED 228 57 245 47

Baseline Characteristics

Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo Total
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study. Total of all reporting groups
Overall Participants 299 303 602
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
64.9
(11.2)
66.3
(10.2)
65.6
(10.7)
Sex: Female, Male (Count of Participants)
Female
39
13%
39
12.9%
78
13%
Male
260
87%
264
87.1%
524
87%
Baseline Eastern Cooperative Oncology Group (ECOG) (participants) [Number]
0 = fully active
161
53.8%
164
54.1%
325
54%
1 = restricted in physical activity but ambulatory
114
38.1%
117
38.6%
231
38.4%
2 = capable of selfcare
24
8%
22
7.3%
46
7.6%
Tumor burden (participants) [Number]
Absent
90
30.1%
91
30%
181
30.1%
Present
209
69.9%
212
70%
421
69.9%

Outcome Measures

1. Primary Outcome
Title Overall Survival (OS)
Description Overall Survival was defined as the time from date of starting treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Time Frame from randomization to death due to any cause until an average 7.2 months later up to the data cut-off date approximately 19 months after start of enrollment

Outcome Measure Data

Analysis Population Description
In this study the overall survival was measured for the ITT population from the date of randomization until the date of death due to any cause. For patients alive or lost to follow-up at the time of analysis, time to death was to be censored at their last date of follow-up, or at the data cut-off of 17 Oct 2006.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Median (95% Confidence Interval) [days]
324
241
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments The 2 arms were compared using a 1-sided log-rank test with an overall alpha of 0.02 stratified by region, ECOG PS and "tumor burden". In addition to the final analysis at the end of the study, 2 formal interim analyses of overall survival were planned. An alpha spending function was used to ensure that the false positive rate is less than or equal to 0.02 (1-sided). The study was stopped at the second interim analysis, the results of which are reported here.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.00583
Comments According to the pre-specified O'Brien-Fleming alpha spending function, the alpha value for this second interim analysis was 0.0073 (corresponding to a nominal value of 0.0077 after taking into account the first interim analysis).
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.6931
Confidence Interval () 95%
0.5549 to 0.8658
Parameter Dispersion Type:
Value:
Estimation Comments This is the sorafenib to placebo hazard ratio.
2. Primary Outcome
Title Time to Symptomatic Progression (TTSP)
Description TTSP was defined as the time from randomization to the first documented symptomatic progression.
Time Frame from randomization to the first documented symptomatic progression until an average 4.8 months later up to the data cut-off date approximately 19 months after start of enrollment

Outcome Measure Data

Analysis Population Description
This analysis was for the ITT population. For subjects who had not progressed symptomatically at the time of interim analysis, TTSP was censored at the date of their last Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index (FHSI-8) questionnaire assessment.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Median (95% Confidence Interval) [days]
126
148
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments The 2 arms were compared using a 1-sided log-rank test with an overall alpha of 0.005 stratified by region, ECOG PS and "tumor burden". This was a co-primary endpoint with overall survival. No alpha-spending adjustments were necessary as it was only to be analyzed at the end of study.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7676
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.0764
Confidence Interval () 95%
0.8837 to 1.3110
Parameter Dispersion Type:
Value:
Estimation Comments This is the sorafenib to placebo hazard ratio.
3. Secondary Outcome
Title Time to Progression (TTP)
Description TTP was defined as the time from randomization to disease progression (radiological only). Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.
Time Frame from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 19 months after start of enrollment

Outcome Measure Data

Analysis Population Description
The primary analysis of TTP for the ITT population was based on the independent radiological review for the interim analysis. The cut-off date chosen for the analysis of radiological progression events was 12 May 2006
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Median (95% Confidence Interval) [days]
168
86
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments In the analysis of TTP, based on independent radiological review performed to review data up to 12 May 2006, the 2 treatment groups were compared using a 1-sided log rank test with an alpha of 0.025, stratified by region, ECOG PS, and "tumor burden".
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.000007
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.5764
Confidence Interval () 95%
0.4484 to 0.7410
Parameter Dispersion Type:
Value:
Estimation Comments This is the sorafenib to placebo hazard ratio.
4. Secondary Outcome
Title Disease Control (DC)
Description The DC is defined as the number of subjects with a best response rating of complete response (CR), partial response (PR), or stable disease (SD) that is maintained at least 28 days from the first manifestation of that rating. Definitions: CR = disappearance of all clinical and radiological tumor lesions; PR = at least 30% decrease in sum of the longest diameters of tumor lesions; SD = neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.
Time Frame time from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment

Outcome Measure Data

Analysis Population Description
In this study, the DC for the ITT population was determined by independent radiological review and also by investigator assessment (both by using response evaluation criteria in solid tumors [RECIST])
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Number [Participants]
130
43.5%
96
31.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments Disease control rates were compared between treatment groups using the Cochran Mantel Haenszel (CMH) test with a 1-sided alpha of 0.025, adjusting for region, ECOG PS, and "tumor burden".
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.001641
Comments
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -11.95
Confidence Interval () 95%
-19.56 to -4.35
Parameter Dispersion Type:
Value:
Estimation Comments Sorafenib minus placebo difference
5. Secondary Outcome
Title Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire
Description PRO is a disease-specific measure, developed as symptom-focused approach in HCC and measured by the response rates for the PWB and FWB subscales of the 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. The FACT-Hep response rate was based on the number of subjects who achieved the 8-point minimally important difference (MID) for this subscale. FACT-Hep total score ranges from 0 to 180, where the highest score represents a maximum achievable quality of life (QoL) value.
Time Frame from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment

Outcome Measure Data

Analysis Population Description
In this study, the PRO was a tertiary efficacy variable assessed for the ITT population at Cycle 3 day 1 or, for those discontinuing prior to that visit, at end of study. It was summarized as number of patients with change from baseline <8 or ≥8 points for each treatment group up to the cutoff date of 17 Oct 2006
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 174 178
Cycle 3 day 1 change <8 points
151
50.5%
139
45.9%
Cycle 3 day 1 change ≥8 points
23
7.7%
39
12.9%
6. Post-Hoc Outcome
Title Overall Survival
Description Overall Survival was defined as the time from date of starting treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Time Frame from randomization to death due to any cause until an average 8.5 months later up to the data cut-off date approximately 23 months after start of enrollment

Outcome Measure Data

Analysis Population Description
The OS data (ITT population) are descriptive only (no p-values) from the date of randomization to the date of death due to any cause. For patients alive at the time of analysis, time to death was censored at the date of last follow-up or at the data cutoff date of 09 Feb 2007 when subjects were given the option to crossover to sorafenib treatment
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Median (95% Confidence Interval) [Days]
327
243
7. Post-Hoc Outcome
Title Time to Symptomatic Progression (TTSP)
Description TTSP was defined as the time from randomization to the first documented symptomatic progression
Time Frame from randomization to the first documented symptomatic progression until an average 5.7 months later up to the data cut-off date approximately 23 months after start of enrollment

Outcome Measure Data

Analysis Population Description
For subjects (in the ITT population) who had not progressed symptomatically at the time of interim analysis, TTSP was censored at the date of last FACT FHSI-8 questionnaire assessment (upon an interim review by the Data Monitoring Committee on 09 Feb 2007), when the study was considered positive for its primary endpoint, OS, and was stopped early.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Median (95% Confidence Interval) [Days]
127
148
8. Post-Hoc Outcome
Title Time to Progression (TTP)
Description TTP was defined as the time from randomization to disease progression (radiological only). Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.
Time Frame from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 23 months after start of enrollment

Outcome Measure Data

Analysis Population Description
The independent radiological review as initially scheduled for the interim analysis did not continue after 12 May 2006. The primary analysis of TTP for the ITT population after 12 May 2006 up to the cutoff date of 09 Feb 2007 was based on the Investigator radiological assessments
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Median (95% Confidence Interval) [Days]
168
86
9. Post-Hoc Outcome
Title Disease Control (DC)
Description The DC is defined as the number of subjects with a best response rating of CR, PR, or SD that is maintained at least 28 days from the first manifestation of that rating.
Time Frame from randomization to end of treatment up to the data cutoff date approximately 23 months after start of enrollment

Outcome Measure Data

Analysis Population Description
The disease control rate for the ITT population was determined by independent radiological review and also by investigator assessment (both by using response evaluation criteria in solid tumors (RECIST) up to the cutoff date of 09 Feb 2007
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 299 303
Number [Participants]
130
43.5%
96
31.7%
10. Post-Hoc Outcome
Title Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire
Description PRO is a disease-specific measure, developed as symptom-focused approach in HCC and measured by the response rates for the PWB and FWB subscales of the 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. The FACT-Hep response rate was based on the number of subjects who achieved the 8-point minimally important difference (MID) for this subscale. FACT-Hep total score ranges from 0 to 180, where the highest score represents a maximum achievable quality of life (QoL) value. At the cut-off date for this analysis, one more patient data has been gained.
Time Frame from randomization to end of treatment up to the data cutoff date approximately 23 months after start of enrollment

Outcome Measure Data

Analysis Population Description
In this study, the PRO was a tertiary efficacy variable assessed for the ITT population at Cycle 3 Day 1 or, for those discontinuing prior to that visit, at the end of study. It was summarized as number of patients with change from baseline <8 to ≥8 points for each treatment group up to the cutoff date of 09 Feb 2007.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Arm/Group Description Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 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. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study. Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
Measure Participants 174 179
Cycle 3 day 1 change <8 points
151
50.5%
139
45.9%
Cycle 3 day 1 change ≥8 points
23
7.7%
40
13.2%

Adverse Events

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 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.
All Cause Mortality
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 153/297 (51.5%) 164/302 (54.3%) 191/297 (64.3%) 185/302 (61.3%) 26/47 (55.3%)
Blood and lymphatic system disorders
neutrophils 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
hemoglobin 8/297 (2.7%) 6/302 (2%) 11/297 (3.7%) 7/302 (2.3%) 0/47 (0%)
leukocytes 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
inr 1/297 (0.3%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
edema: limb 2/297 (0.7%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
lymphatics - other 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
lymphedema-related fibrosis 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
edema: head and neck 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
Cardiac disorders
supraventricular arrhythmia, atrial fibrillation 1/297 (0.3%) 2/302 (0.7%) 1/297 (0.3%) 3/302 (1%) 0/47 (0%)
conduction abnormality, av block - first degree 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
supraventricular arrhythmia, sinus tachycardia 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
ventricular arrhythmia, ventricular fibrillation 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
ventricular arrhythmia, ventricular tachycardia 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
left ventricular diastolic dysfunction 2/297 (0.7%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
hypertension 1/297 (0.3%) 1/302 (0.3%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
cardiac ischemia/infarction 8/297 (2.7%) 4/302 (1.3%) 9/297 (3%) 5/302 (1.7%) 1/47 (2.1%)
hypotension 1/297 (0.3%) 2/302 (0.7%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
cardiac general - other 0/297 (0%) 3/302 (1%) 0/297 (0%) 3/302 (1%) 0/47 (0%)
right ventricular dysfunction 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
left ventricular systolic dysfunction 1/297 (0.3%) 2/302 (0.7%) 2/297 (0.7%) 2/302 (0.7%) 0/47 (0%)
conduction abnormality, asystole 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
conduction abnormality, av block-3rd degree (complete av block 0/297 (0%) 0/302 (0%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
cardiac arrhythmia - other 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
cardiopulmonary arrest 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
Endocrine disorders
hyperthyroidism 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
adrenal insufficiency 0/297 (0%) 0/302 (0%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
Eye disorders
retinal detachment 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
Gastrointestinal disorders
anorexia 3/297 (1%) 1/302 (0.3%) 3/297 (1%) 1/302 (0.3%) 0/47 (0%)
ascites 14/297 (4.7%) 13/302 (4.3%) 16/297 (5.4%) 20/302 (6.6%) 4/47 (8.5%)
colitis 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 0/302 (0%) 0/47 (0%)
constipation 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
dehydration 9/297 (3%) 1/302 (0.3%) 10/297 (3.4%) 1/302 (0.3%) 0/47 (0%)
diarrhea 14/297 (4.7%) 5/302 (1.7%) 16/297 (5.4%) 5/302 (1.7%) 1/47 (2.1%)
dysphagia 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
enteritis 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
gastritis 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
nausea 0/297 (0%) 4/302 (1.3%) 0/297 (0%) 3/302 (1%) 0/47 (0%)
gi - other 4/297 (1.3%) 0/302 (0%) 6/297 (2%) 0/302 (0%) 1/47 (2.1%)
perforation, gi, colon 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
stricture, gi, biliary tree 0/297 (0%) 1/302 (0.3%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
ulcer, gi, duodenum 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 1/47 (2.1%)
ulcer, gi, stomach 1/297 (0.3%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
vomiting 5/297 (1.7%) 4/302 (1.3%) 5/297 (1.7%) 4/302 (1.3%) 0/47 (0%)
cholecystitis 1/297 (0.3%) 0/302 (0%) 3/297 (1%) 0/302 (0%) 0/47 (0%)
liver dysfunction 21/297 (7.1%) 14/302 (4.6%) 21/297 (7.1%) 18/302 (6%) 1/47 (2.1%)
hepatobiliary - other 11/297 (3.7%) 16/302 (5.3%) 16/297 (5.4%) 22/302 (7.3%) 5/47 (10.6%)
pancreatitis 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
distension 0/297 (0%) 0/302 (0%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
obstruction, gi, small bowel nos 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
perforation, gi, appendix 0/297 (0%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 1/47 (2.1%)
General disorders
death not associated with ctcae term, death nos 1/297 (0.3%) 4/302 (1.3%) 1/297 (0.3%) 5/302 (1.7%) 1/47 (2.1%)
death not associated with ctcae term, disease progression nos 56/297 (18.9%) 61/302 (20.2%) 68/297 (22.9%) 66/302 (21.9%) 10/47 (21.3%)
death not associated with ctcae term, multi-organ failure 1/297 (0.3%) 0/302 (0%) 4/297 (1.3%) 0/302 (0%) 0/47 (0%)
death not associated with ctcae term, sudden death 0/297 (0%) 1/302 (0.3%) 1/297 (0.3%) 1/302 (0.3%) 1/47 (2.1%)
fever 3/297 (1%) 4/302 (1.3%) 4/297 (1.3%) 4/302 (1.3%) 1/47 (2.1%)
insomnia 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 0/302 (0%) 0/47 (0%)
fatigue 5/297 (1.7%) 9/302 (3%) 7/297 (2.4%) 6/302 (2%) 1/47 (2.1%)
weight loss 0/297 (0%) 3/302 (1%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
constitutional symptoms - other 3/297 (1%) 6/302 (2%) 6/297 (2%) 8/302 (2.6%) 2/47 (4.3%)
pain, back 3/297 (1%) 3/302 (1%) 3/297 (1%) 4/302 (1.3%) 0/47 (0%)
pain, extremity-limb 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
pain, tumor pain 1/297 (0.3%) 1/302 (0.3%) 2/297 (0.7%) 1/302 (0.3%) 0/47 (0%)
pain, abdomen nos 7/297 (2.4%) 8/302 (2.6%) 10/297 (3.4%) 9/302 (3%) 0/47 (0%)
pain, joint 3/297 (1%) 0/302 (0%) 3/297 (1%) 1/302 (0.3%) 0/47 (0%)
pain, bone 3/297 (1%) 1/302 (0.3%) 3/297 (1%) 1/302 (0.3%) 0/47 (0%)
pain, other 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
pain, liver 0/297 (0%) 2/302 (0.7%) 0/297 (0%) 3/302 (1%) 0/47 (0%)
pain, neuralgia/peripheral nerve 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
pain, stomach 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 0/302 (0%) 0/47 (0%)
syndromes - other 2/297 (0.7%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
not coded yet 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 0/302 (0%) 0/47 (0%)
pain, chest/thorax nos 0/297 (0%) 0/302 (0%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
tumor flare 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
Infections and infestations
infection (documented clinically), abdomen nos 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection (documented clinically), anal/perianal 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection (documented clinically), biliary tree 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
infection (documented clinically), lung (pneumonia) 3/297 (1%) 3/302 (1%) 6/297 (2%) 4/302 (1.3%) 2/47 (4.3%)
infection (documented clinically), skin (cellulitis) 1/297 (0.3%) 1/302 (0.3%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
infection (documented clinically), soft tissue nos 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
infection (documented clinically), upper airway nos 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection (documented clinically), urinary tract nos 3/297 (1%) 0/302 (0%) 3/297 (1%) 0/302 (0%) 0/47 (0%)
infection with normal anc, bronchus 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
infection with normal anc, gallbladder (cholecystitis) 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection with normal anc, oral cavity-gums (gingivitis) 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
infection with normal anc, peritoneal cavity 0/297 (0%) 2/302 (0.7%) 0/297 (0%) 2/302 (0.7%) 0/47 (0%)
infection with normal anc, skin (cellulitis) 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
infection with normal anc, urinary tract nos 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
infection - other 0/297 (0%) 3/302 (1%) 2/297 (0.7%) 4/302 (1.3%) 0/47 (0%)
infection with unknown anc, biliary tree 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection with unknown anc, lung (pneumonia) 0/297 (0%) 3/302 (1%) 0/297 (0%) 4/302 (1.3%) 0/47 (0%)
infection with unknown anc, peritoneal cavity 1/297 (0.3%) 2/302 (0.7%) 1/297 (0.3%) 2/302 (0.7%) 0/47 (0%)
infection with unknown anc, urinary tract nos 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
infection with unknown anc, wound 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection (documented clinically), blood 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection with normal anc, anal/perianal 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection with normal anc, appendix 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection with normal anc, pancreas 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection with unknown anc, appendix 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
infection with unknown anc, blood 0/297 (0%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 1/47 (2.1%)
infection with unknown anc, bronchus 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
Injury, poisoning and procedural complications
intraop injury, biliary tree - common bile duct 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
Metabolism and nutrition disorders
ALT 0/297 (0%) 2/302 (0.7%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
AST 1/297 (0.3%) 2/302 (0.7%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
cpk 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
creatinine 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 2/302 (0.7%) 1/47 (2.1%)
ggt 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
bilirubin (hyperbilirubinemia) 6/297 (2%) 4/302 (1.3%) 6/297 (2%) 5/302 (1.7%) 1/47 (2.1%)
hypercalcemia 2/297 (0.7%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
hyperglycemia 1/297 (0.3%) 1/302 (0.3%) 1/297 (0.3%) 2/302 (0.7%) 0/47 (0%)
hyperkalemia 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
hypoalbuminemia 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
hypoglycemia 5/297 (1.7%) 3/302 (1%) 5/297 (1.7%) 3/302 (1%) 1/47 (2.1%)
hypomagnesemia 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 1/47 (2.1%)
hyponatremia 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
hypocalcemia 0/297 (0%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 1/47 (2.1%)
hypokalemia 0/297 (0%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 1/47 (2.1%)
Musculoskeletal and connective tissue disorders
fracture 4/297 (1.3%) 3/302 (1%) 5/297 (1.7%) 4/302 (1.3%) 1/47 (2.1%)
musculoskeletal - other 2/297 (0.7%) 3/302 (1%) 3/297 (1%) 3/302 (1%) 0/47 (0%)
device/prosthesis 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
muscle weakness, whole body/generalized 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
Nervous system disorders
cns ischemia 0/297 (0%) 4/302 (1.3%) 1/297 (0.3%) 4/302 (1.3%) 2/47 (4.3%)
confusion 1/297 (0.3%) 1/302 (0.3%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
dizziness 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
encephalopathy 2/297 (0.7%) 2/302 (0.7%) 4/297 (1.3%) 3/302 (1%) 1/47 (2.1%)
mood alteration, depression 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
neuropathy: motor 1/297 (0.3%) 3/302 (1%) 1/297 (0.3%) 3/302 (1%) 0/47 (0%)
neurology - other 0/297 (0%) 3/302 (1%) 0/297 (0%) 3/302 (1%) 0/47 (0%)
neuropathy: sensory 1/297 (0.3%) 1/302 (0.3%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
seizure 1/297 (0.3%) 2/302 (0.7%) 1/297 (0.3%) 2/302 (0.7%) 0/47 (0%)
somnolence 2/297 (0.7%) 2/302 (0.7%) 2/297 (0.7%) 2/302 (0.7%) 0/47 (0%)
syncope (fainting) 2/297 (0.7%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
cognitive disturbance 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
Renal and urinary disorders
renal failure 1/297 (0.3%) 8/302 (2.6%) 2/297 (0.7%) 8/302 (2.6%) 1/47 (2.1%)
obstruction, gu, ureter 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
urinary retention 0/297 (0%) 0/302 (0%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
Respiratory, thoracic and mediastinal disorders
pleural effusion 1/297 (0.3%) 1/302 (0.3%) 2/297 (0.7%) 1/302 (0.3%) 1/47 (2.1%)
hiccoughs 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
hypoxia 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
pulmonary - other 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
pneumothorax 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
dyspnea (shortness of breath) 3/297 (1%) 2/302 (0.7%) 3/297 (1%) 2/302 (0.7%) 0/47 (0%)
Skin and subcutaneous tissue disorders
hand-foot skin reaction 2/297 (0.7%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
dermatology - other 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 1/47 (2.1%)
pruritus 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
decubitus 0/297 (0%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 1/47 (2.1%)
wound complication, non-infectious 0/297 (0%) 0/302 (0%) 2/297 (0.7%) 0/302 (0%) 0/47 (0%)
rash/desquamation 0/297 (0%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 1/47 (2.1%)
ulceration 0/297 (0%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 1/47 (2.1%)
Vascular disorders
cns hemorrhage 2/297 (0.7%) 1/302 (0.3%) 2/297 (0.7%) 1/302 (0.3%) 0/47 (0%)
hematoma 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
hemorrhage, gi, abdomen nos 2/297 (0.7%) 3/302 (1%) 2/297 (0.7%) 3/302 (1%) 0/47 (0%)
hemorrhage, gi, colon 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
hemorrhage, gi, duodenum 1/297 (0.3%) 2/302 (0.7%) 1/297 (0.3%) 3/302 (1%) 0/47 (0%)
hemorrhage, gi, esophagus 2/297 (0.7%) 3/302 (1%) 4/297 (1.3%) 4/302 (1.3%) 1/47 (2.1%)
hemorrhage, gi, varices (esophageal) 7/297 (2.4%) 11/302 (3.6%) 8/297 (2.7%) 13/302 (4.3%) 1/47 (2.1%)
hemorrhage, gi, stomach 4/297 (1.3%) 2/302 (0.7%) 5/297 (1.7%) 2/302 (0.7%) 0/47 (0%)
hemorrhage, gi, liver 4/297 (1.3%) 1/302 (0.3%) 6/297 (2%) 1/302 (0.3%) 0/47 (0%)
hemorrhage, gi, lower gi nos 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
hemorrhage, gi, oral cavity 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
hemorrhage, gi, peritoneal cavity 0/297 (0%) 6/302 (2%) 2/297 (0.7%) 8/302 (2.6%) 0/47 (0%)
hemorrhage, gi, varices (rectal) 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
hemorrhage, gi, upper gi nos 3/297 (1%) 6/302 (2%) 5/297 (1.7%) 6/302 (2%) 0/47 (0%)
hemorrhage with surgery 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
hemorrhage - other 1/297 (0.3%) 1/302 (0.3%) 2/297 (0.7%) 1/302 (0.3%) 0/47 (0%)
hemorrhage pulmonary, lung 1/297 (0.3%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 0/47 (0%)
hemorrhage pulmonary, pleura 0/297 (0%) 1/302 (0.3%) 0/297 (0%) 1/302 (0.3%) 0/47 (0%)
peripheral arterial ischemia 1/297 (0.3%) 0/302 (0%) 0/297 (0%) 0/302 (0%) 0/47 (0%)
thrombosis/thrombus/embolism 3/297 (1%) 3/302 (1%) 7/297 (2.4%) 5/302 (1.7%) 1/47 (2.1%)
visceral arterial ischemia 1/297 (0.3%) 1/302 (0.3%) 1/297 (0.3%) 1/302 (0.3%) 0/47 (0%)
hemorrhage, gi, rectum 0/297 (0%) 0/302 (0%) 1/297 (0.3%) 0/302 (0%) 1/47 (2.1%)
Other (Not Including Serious) Adverse Events
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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 275/297 (92.6%) 259/302 (85.8%) 281/297 (94.6%) 271/302 (89.7%) 43/47 (91.5%)
Blood and lymphatic system disorders
hemoglobin 25/297 (8.4%) 22/302 (7.3%) 36/297 (12.1%) 25/302 (8.3%) 5/47 (10.6%)
edema: limb 45/297 (15.2%) 53/302 (17.5%) 59/297 (19.9%) 57/302 (18.9%) 9/47 (19.1%)
platelets 9/297 (3%) 7/302 (2.3%) 15/297 (5.1%) 8/302 (2.6%) 0/47 (0%)
Cardiac disorders
hypertension 27/297 (9.1%) 12/302 (4%) 32/297 (10.8%) 13/302 (4.3%) 6/47 (12.8%)
Gastrointestinal disorders
anorexia 83/297 (27.9%) 52/302 (17.2%) 89/297 (30%) 56/302 (18.5%) 8/47 (17%)
ascites 61/297 (20.5%) 67/302 (22.2%) 80/297 (26.9%) 67/302 (22.2%) 9/47 (19.1%)
constipation 41/297 (13.8%) 31/302 (10.3%) 44/297 (14.8%) 32/302 (10.6%) 3/47 (6.4%)
diarrhea 158/297 (53.2%) 74/302 (24.5%) 166/297 (55.9%) 82/302 (27.2%) 22/47 (46.8%)
heartburn 15/297 (5.1%) 10/302 (3.3%) 16/297 (5.4%) 10/302 (3.3%) 1/47 (2.1%)
mucositis (functional/symptomatic), oral cavity 15/297 (5.1%) 6/302 (2%) 16/297 (5.4%) 8/302 (2.6%) 0/47 (0%)
mucositis (clinical exam), oral cavity 16/297 (5.4%) 10/302 (3.3%) 19/297 (6.4%) 10/302 (3.3%) 1/47 (2.1%)
nausea 71/297 (23.9%) 58/302 (19.2%) 73/297 (24.6%) 63/302 (20.9%) 8/47 (17%)
gi - other 16/297 (5.4%) 10/302 (3.3%) 22/297 (7.4%) 13/302 (4.3%) 3/47 (6.4%)
vomiting 41/297 (13.8%) 30/302 (9.9%) 48/297 (16.2%) 34/302 (11.3%) 4/47 (8.5%)
liver dysfunction 18/297 (6.1%) 9/302 (3%) 21/297 (7.1%) 10/302 (3.3%) 1/47 (2.1%)
dry mouth 12/297 (4%) 9/302 (3%) 14/297 (4.7%) 9/302 (3%) 3/47 (6.4%)
hemorrhoids 7/297 (2.4%) 2/302 (0.7%) 8/297 (2.7%) 3/302 (1%) 3/47 (6.4%)
hepatobiliary - other 12/297 (4%) 14/302 (4.6%) 17/297 (5.7%) 17/302 (5.6%) 2/47 (4.3%)
General disorders
fever 29/297 (9.8%) 28/302 (9.3%) 35/297 (11.8%) 30/302 (9.9%) 2/47 (4.3%)
insomnia 21/297 (7.1%) 22/302 (7.3%) 26/297 (8.8%) 23/302 (7.6%) 5/47 (10.6%)
fatigue 133/297 (44.8%) 132/302 (43.7%) 145/297 (48.8%) 144/302 (47.7%) 23/47 (48.9%)
weight loss 89/297 (30%) 28/302 (9.3%) 93/297 (31.3%) 31/302 (10.3%) 10/47 (21.3%)
pain, back 36/297 (12.1%) 38/302 (12.6%) 47/297 (15.8%) 42/302 (13.9%) 4/47 (8.5%)
pain, abdomen nos 91/297 (30.6%) 74/302 (24.5%) 99/297 (33.3%) 80/302 (26.5%) 11/47 (23.4%)
pain, head/headache 26/297 (8.8%) 25/302 (8.3%) 29/297 (9.8%) 25/302 (8.3%) 1/47 (2.1%)
pain, joint 20/297 (6.7%) 26/302 (8.6%) 20/297 (6.7%) 27/302 (8.9%) 1/47 (2.1%)
pain, stomach 21/297 (7.1%) 20/302 (6.6%) 23/297 (7.7%) 21/302 (7%) 2/47 (4.3%)
constitutional symptoms - other 7/297 (2.4%) 10/302 (3.3%) 12/297 (4%) 12/302 (4%) 4/47 (8.5%)
pain, bone 12/297 (4%) 13/302 (4.3%) 16/297 (5.4%) 15/302 (5%) 0/47 (0%)
pain, liver 12/297 (4%) 13/302 (4.3%) 13/297 (4.4%) 16/302 (5.3%) 1/47 (2.1%)
flu-like syndrome 8/297 (2.7%) 7/302 (2.3%) 9/297 (3%) 8/302 (2.6%) 3/47 (6.4%)
Infections and infestations
infection - other 6/297 (2%) 3/302 (1%) 16/297 (5.4%) 6/302 (2%) 8/47 (17%)
Metabolism and nutrition disorders
AST 8/297 (2.7%) 18/302 (6%) 9/297 (3%) 20/302 (6.6%) 1/47 (2.1%)
bilirubin (hyperbilirubinemia) 24/297 (8.1%) 23/302 (7.6%) 28/297 (9.4%) 26/302 (8.6%) 1/47 (2.1%)
Musculoskeletal and connective tissue disorders
musculoskeletal - other 24/297 (8.1%) 15/302 (5%) 31/297 (10.4%) 18/302 (6%) 1/47 (2.1%)
Nervous system disorders
mood alteration, depression 10/297 (3.4%) 7/302 (2.3%) 14/297 (4.7%) 9/302 (3%) 7/47 (14.9%)
Respiratory, thoracic and mediastinal disorders
cough 24/297 (8.1%) 16/302 (5.3%) 26/297 (8.8%) 18/302 (6%) 3/47 (6.4%)
dyspnea (shortness of breath) 26/297 (8.8%) 22/302 (7.3%) 33/297 (11.1%) 24/302 (7.9%) 3/47 (6.4%)
voice changes 27/297 (9.1%) 4/302 (1.3%) 27/297 (9.1%) 5/302 (1.7%) 1/47 (2.1%)
Skin and subcutaneous tissue disorders
alopecia 42/297 (14.1%) 5/302 (1.7%) 46/297 (15.5%) 6/302 (2%) 6/47 (12.8%)
dry skin 31/297 (10.4%) 18/302 (6%) 31/297 (10.4%) 18/302 (6%) 3/47 (6.4%)
hand-foot skin reaction 63/297 (21.2%) 9/302 (3%) 67/297 (22.6%) 9/302 (3%) 6/47 (12.8%)
dermatology - other 26/297 (8.8%) 12/302 (4%) 30/297 (10.1%) 15/302 (5%) 5/47 (10.6%)
pruritus 40/297 (13.5%) 33/302 (10.9%) 44/297 (14.8%) 35/302 (11.6%) 5/47 (10.6%)
rash/desquamation 55/297 (18.5%) 42/302 (13.9%) 59/297 (19.9%) 46/302 (15.2%) 6/47 (12.8%)
erythema multiforme 1/297 (0.3%) 3/302 (1%) 1/297 (0.3%) 4/302 (1.3%) 3/47 (6.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title Therapeutic Area Head
Organization BAYER
Phone
Email clinical-trials-contact@bayerhealthcare.com
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00105443
Other Study ID Numbers:
  • 100554
  • 2004-001773-26
First Posted:
Mar 15, 2005
Last Update Posted:
Oct 31, 2014
Last Verified:
Oct 1, 2014