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A Study In Patients With Non-Small Cell Lung Cancer To Test If Erlotinib Plus SU011248 Is Better Than Erlotinib Alone

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00457392
Collaborator
(none)
960
Enrollment
204
Locations
2
Arms
65.1
Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will test whether treatment with erlotinib plus SU011248 is better than erlotinib alone in patients with advanced/metastatic lung cancer who have received previous treatment with a platinum-based regimen.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
960 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Controlled Phase 3, Efficacy And Safety Study Of Sunitinib (SU011248) In Patients With Advanced/Metastatic Non-Small Cell Lung Cancer Treated With Erlotinib
Study Start Date :
Jul 1, 2007
Actual Primary Completion Date :
Jul 1, 2010
Actual Study Completion Date :
Dec 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Drug: erlotinib
plus erlotinib 150 mg daily by tablets in a continuous regimen until progression or unacceptable toxicity

Drug: sunitinib
Sunitinib 37.5 mg daily by oral capsules in a continuous regimen
Active Comparator: 2

Drug: erlotinib
plus erlotinib 150 mg daily by tablets in a continuous regimen until progression or unacceptable toxicity

Drug: placebo
Placebo daily by oral capsules in a continuous regimen

Outcome Measures

Primary Outcome Measures

  1. Overall Survival (OS) [Baseline to death or 28 days after last dose for the last participant]

    Overall survival is the duration from assignment to study medication to death. For participants who are alive, overall survival is censored at the last contact.

Secondary Outcome Measures

  1. Progression-Free Survival (PFS) [Baseline to disease progression or death due to any cause or 28 days after last dose]

    Time in weeks from assignment to study medication to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

  2. Percentage of Participants With Objective Response (OR) [Baseline to disease progression or discontinuation from study or 28 days after last dose]

    Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.

  3. Duration of Response (DR) [Baseline to disease progression or death or discontinuation from study or 28 days after last dose]

    Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7.

  4. One-year Survival Probability [Baseline until death or until 28 days after last dose for the last participant]

    The 1 year survival probability was defined as the probability of survival at one year after the date of the start of the study treatment based on the Kaplan Meier estimate.

  5. EuroQol 5-Dimension Questionnaire (EQ-5D)- Health State Profile Utility Score [Baseline and End of Treatment (EOT) or Withdrawal]

    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates better health state.

Eligibility Criteria

Criteria

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

  • Patients with locally advanced/metastatic non-small cell lung cancer

  • Prior treatment with no more than 2 chemotherapy regimens including a platinum-based regimen

Exclusion Criteria:

  • Prior treatment with any receptor tyrosine kinase inhibitors, VEGF inhibitor (with the exception of bevacizumab) or other angiogenesis inhibitors

  • History of or known brain metastases

Contacts and Locations

Locations

Site City State Country Postal Code
1 Pfizer Investigational Site Florence Alabama United States 35630
2 Pfizer Investigational Site Muscle Shoals Alabama United States 35661
3 Pfizer Investigational Site Scottsdale Arizona United States 85258
4 Pfizer Investigational Site Hot Springs Arkansas United States 71913
5 Pfizer Investigational Site Antioch California United States 94531
6 Pfizer Investigational Site Burbank California United States 91505-4866
7 Pfizer Investigational Site Downey California United States 90241
8 Pfizer Investigational Site Fresno California United States 93720
9 Pfizer Investigational Site La Jolla California United States 92037
10 Pfizer Investigational Site La Jolla California United States 92093-0987
11 Pfizer Investigational Site Montebello California United States 90640
12 Pfizer Investigational Site Pleasant Hill California United States 94523
13 Pfizer Investigational Site San Diego California United States 92103
14 Pfizer Investigational Site San Leandro California United States 94578
15 Pfizer Investigational Site Whittier California United States 90606
16 Pfizer Investigational Site Fairfield Connecticut United States 06824
17 Pfizer Investigational Site Brooksville Florida United States 34613
18 Pfizer Investigational Site Cocoa Beach Florida United States 32931
19 Pfizer Investigational Site Fort Lauderdale Florida United States 33308
20 Pfizer Investigational Site Merritt Island Florida United States 32952
21 Pfizer Investigational Site Rockledge Florida United States 32955
22 Pfizer Investigational Site Titusville Florida United States 32796
23 Pfizer Investigational Site Athens Georgia United States 30607
24 Pfizer Investigational Site Aurora Illinois United States 60504
25 Pfizer Investigational Site Goshen Indiana United States 46526
26 Pfizer Investigational Site Indianapolis Indiana United States 46260-2082
27 Pfizer Investigational Site Council Bluffs Iowa United States 51503
28 Pfizer Investigational Site Baton Rouge Louisiana United States 70809
29 Pfizer Investigational Site Lafayette Louisiana United States 70503
30 Pfizer Investigational Site Bethesda Maryland United States 20817
31 Pfizer Investigational Site Ann Arbor Michigan United States 48106
32 Pfizer Investigational Site Troy Michigan United States 48085
33 Pfizer Investigational Site Columbus Mississippi United States 39705
34 Pfizer Investigational Site Corinth Mississippi United States 38834
35 Pfizer Investigational Site Tupelo Mississippi United States 38801
36 Pfizer Investigational Site St. Louis Missouri United States 63110
37 Pfizer Investigational Site St. Peters Missouri United States 63376
38 Pfizer Investigational Site Omaha Nebraska United States 68105
39 Pfizer Investigational Site Las Vegas Nevada United States 89102
40 Pfizer Investigational Site Las Vegas Nevada United States 89106
41 Pfizer Investigational Site Jamaica New York United States 11432
42 Pfizer Investigational Site Norman Oklahoma United States 73071
43 Pfizer Investigational Site Oklahoma City Oklahoma United States 73102
44 Pfizer Investigational Site Oklahoma City Oklahoma United States 73109
45 Pfizer Investigational Site Oklahoma City Oklahoma United States 73120
46 Pfizer Investigational Site Tulsa Oklahoma United States 74014
47 Pfizer Investigational Site Tulsa Oklahoma United States 74104
48 Pfizer Investigational Site Tulsa Oklahoma United States 74136
49 Pfizer Investigational Site Lancaster Pennsylvania United States 17605
50 Pfizer Investigational Site Knoxville Tennessee United States 37920
51 Pfizer Investigational Site Beaumont Texas United States 77701
52 Pfizer Investigational Site Dallas Texas United States 75231
53 Pfizer Investigational Site Grapevine Texas United States 76051
54 Pfizer Investigational Site Irving Texas United States 75063
55 Pfizer Investigational Site Bountiful Utah United States 84010
56 Pfizer Investigational Site Layton Utah United States 84041
57 Pfizer Investigational Site Murray Utah United States 84157
58 Pfizer Investigational Site Provo Utah United States 84604
59 Pfizer Investigational Site Salt Lake City Utah United States 84102
60 Pfizer Investigational Site Salt Lake City Utah United States 84106
61 Pfizer Investigational Site Sandy Utah United States 84094
62 Pfizer Investigational Site West Valley Utah United States 84102
63 Pfizer Investigational Site Kennewick Washington United States 99336
64 Pfizer Investigational Site Buenos Aires Capital Federal Argentina C1122AAL
65 Pfizer Investigational Site Ciudad Autonoma de Buenos Aires Capital Federal Argentina C1094AAD
66 Pfizer Investigational Site Buenos Aires Argentina C1034ACO
67 Pfizer Investigational Site Cordoba Argentina 5000
68 Pfizer Investigational Site Grimmenstein Austria A-2840
69 Pfizer Investigational Site Innsbruck Austria A-6020
70 Pfizer Investigational Site Linz Austria A-4010
71 Pfizer Investigational Site Bruxelles Belgium 1070
72 Pfizer Investigational Site Leuven Belgium 3000
73 Pfizer Investigational Site Liege Belgium 4000
74 Pfizer Investigational Site Rio de Janeiro RJ Brazil 20230-130
75 Pfizer Investigational Site Rio de Janeiro RJ Brazil 20231 -050
76 Pfizer Investigational Site Porto Alegre RS Brazil 90840-440
77 Pfizer Investigational Site Barretos SP Brazil 14784-400
78 Pfizer Investigational Site Sao Paulo SP Brazil 01308-050
79 Pfizer Investigational Site Kingston Ontario Canada K7L 2V7
80 Pfizer Investigational Site Kingston Ontario Canada K7L 5P9
81 Pfizer Investigational Site Oshawa Ontario Canada L1G 2B9
82 Pfizer Investigational Site Toronto Ontario Canada M4N 3M5
83 Pfizer Investigational Site Toronto Ontario Canada M5G 2M9
84 Pfizer Investigational Site Greenfield Park Quebec Canada J4V 2H1
85 Pfizer Investigational Site Levis Quebec Canada G6V 3Z1
86 Pfizer Investigational Site Rimouski Quebec Canada G5L 5T1
87 Pfizer Investigational Site Saskatoon Saskatchewan Canada S7N 4H4
88 Pfizer Investigational Site Quebec Canada G1J 1Z4
89 Pfizer Investigational Site Independencia Santiago, RM Chile 8380456
90 Pfizer Investigational Site Providencia Santiago, RM Chile 7500921
91 Pfizer Investigational Site Santiago Chile
92 Pfizer Investigational Site Medellin Antioquia Colombia 0
93 Pfizer Investigational Site Medellin Antioquia Colombia
94 Pfizer Investigational Site Ceske Budejovice Czech Republic 370 87
95 Pfizer Investigational Site Nova Ves pod Plesi Czech Republic 262 04
96 Pfizer Investigational Site Olomouc Czech Republic 775 20
97 Pfizer Investigational Site Ostrava-Poruba Czech Republic 708 52
98 Pfizer Investigational Site Praha 2 Czech Republic 128 08
99 Pfizer Investigational Site Praha 8 Czech Republic 180 81
100 Pfizer Investigational Site Pribram V Czech Republic 261 95
101 Pfizer Investigational Site Tabor Czech Republic 390 03
102 Pfizer Investigational Site Usti nad Labem Czech Republic 401 13
103 Pfizer Investigational Site Herlev Denmark 2730
104 Pfizer Investigational Site Hilleroed Denmark 3400
105 Pfizer Investigational Site Koebenhavn OE Denmark 2100
106 Pfizer Investigational Site Odense Denmark 5000
107 Pfizer Investigational Site Bad Berka Germany 99437
108 Pfizer Investigational Site Berlin Germany 12203
109 Pfizer Investigational Site Dresden Germany 01307
110 Pfizer Investigational Site Ebensfeld Germany 96250
111 Pfizer Investigational Site Essen Germany 45122
112 Pfizer Investigational Site Gauting Germany 82131
113 Pfizer Investigational Site Grosshansdorf Germany 22927
114 Pfizer Investigational Site Halle (Saale) Germany 06120
115 Pfizer Investigational Site Heidelberg Germany 69126
116 Pfizer Investigational Site Homburg Germany 66424
117 Pfizer Investigational Site Mainz Germany 55131
118 Pfizer Investigational Site Tuebingen Germany 72076
119 Pfizer Investigational Site Wiesbaden Germany 65199
120 Pfizer Investigational Site Heraklion Crete Greece 71 110
121 Pfizer Investigational Site Alexandroupoli Greece 68100
122 Pfizer Investigational Site Athens Greece 11527
123 Pfizer Investigational Site Kifisia, Athens Greece 145 64
124 Pfizer Investigational Site Kowloon Hong Kong
125 Pfizer Investigational Site Shatin, NT Hong Kong
126 Pfizer Investigational Site Tuen Mun, Hong Kong
127 Pfizer Investigational Site Budapest Hungary H-1529
128 Pfizer Investigational Site Deszk Hungary 6772
129 Pfizer Investigational Site Gyula Hungary 5703
130 Pfizer Investigational Site Matrahaza Hungary H-3233
131 Pfizer Investigational Site Szekesfehervar Hungary 8000
132 Pfizer Investigational Site Zalaegerszeg-Pozva Hungary H-8900
133 Pfizer Investigational Site Catania Italy 95122
134 Pfizer Investigational Site Grosseto Italy 58100
135 Pfizer Investigational Site Mantova Italy 46100
136 Pfizer Investigational Site Milano Italy 20132
137 Pfizer Investigational Site Milano Italy 20162
138 Pfizer Investigational Site Monza (MI) Italy 20052
139 Pfizer Investigational Site Novara Italy 28100
140 Pfizer Investigational Site Orbassano (TO) Italy 10043
141 Pfizer Investigational Site Parma Italy 43100
142 Pfizer Investigational Site Roma Italy 00152
143 Pfizer Investigational Site Rozzano (MI) Italy 20089
144 Pfizer Investigational Site Seoul Korea, Republic of 120-725
145 Pfizer Investigational Site Seoul Korea, Republic of 120-752
146 Pfizer Investigational Site Seoul Korea, Republic of 135-710
147 Pfizer Investigational Site Seoul Korea, Republic of 138-736
148 Pfizer Investigational Site Enschede Ov Netherlands 7513 ER
149 Pfizer Investigational Site 's-Hertogenbosch Netherlands 5211 RW
150 Pfizer Investigational Site Amsterdam Netherlands 1081 HV
151 Pfizer Investigational Site Arnhem Netherlands 6815 AD
152 Pfizer Investigational Site Harderwijk Netherlands 3844 DG
153 Pfizer Investigational Site Maastricht Netherlands 6229 HX
154 Pfizer Investigational Site Rotterdam Netherlands 3075 EA
155 Pfizer Investigational Site Rotterdam Netherlands 3097 DZ
156 Pfizer Investigational Site Kristiansand S Norway 4604
157 Pfizer Investigational Site Oslo Norway 0379
158 Pfizer Investigational Site Stavanger Norway 4011
159 Pfizer Investigational Site Tromso Norway 9038
160 Pfizer Investigational Site Trondheim Norway 7030
161 Pfizer Investigational Site Lodz Poland 93-509
162 Pfizer Investigational Site Opole Poland 45-060
163 Pfizer Investigational Site Otwock Poland 05-400
164 Pfizer Investigational Site Warszawa Poland 01-138
165 Pfizer Investigational Site Warszawa Poland 02-781
166 Pfizer Investigational Site Zielona Gora Poland 65-046
167 Pfizer Investigational Site Moscow Russian Federation 115478
168 Pfizer Investigational Site Moscow Russian Federation 143423
169 Pfizer Investigational Site St-Petersburg Russian Federation 194044
170 Pfizer Investigational Site St. Petersburg Russian Federation 197022
171 Pfizer Investigational Site Bratislava Slovakia 826 06
172 Pfizer Investigational Site Kosice Slovakia 041 90
173 Pfizer Investigational Site Kvetnica pri Poprade Slovakia 058 87
174 Pfizer Investigational Site Nitra-Zobor Slovakia 949 88
175 Pfizer Investigational Site Zilina Slovakia 012 07
176 Pfizer Investigational Site Sabadell Barcelona Spain 08208
177 Pfizer Investigational Site Palma de Mallorca Islas Baleares Spain 07198
178 Pfizer Investigational Site La Laguna Santa Cruz de Tenerife Spain 38320
179 Pfizer Investigational Site Dos Hermanas Sevilla Spain 41700
180 Pfizer Investigational Site Barcelona Spain 08036
181 Pfizer Investigational Site La Coruña Spain 15006
182 Pfizer Investigational Site Madrid Spain 28046
183 Pfizer Investigational Site Malaga Spain 29010
184 Pfizer Investigational Site Sevilla Spain 41013
185 Pfizer Investigational Site Valencia Spain 46015
186 Pfizer Investigational Site Genolier Switzerland 1272
187 Pfizer Investigational Site Gwei Shan Township Taoyuan County Taiwan 333
188 Pfizer Investigational Site Taichung Taiwan 40705
189 Pfizer Investigational Site Tainan Taiwan 704
190 Pfizer Investigational Site Pathumwan Bangkok Thailand 10330
191 Pfizer Investigational Site Amphoe Mueang Chiang Mai Thailand 50200
192 Pfizer Investigational Site Bangkok Thailand 10700
193 Pfizer Investigational Site Bebington, Wirral United Kingdom CH63 4JY
194 Pfizer Investigational Site Cambridge United Kingdom CB2 0QQ
195 Pfizer Investigational Site Derby United Kingdom DE1 2QY
196 Pfizer Investigational Site Dundee United Kingdom DD1 9SY
197 Pfizer Investigational Site Keighley, West Yorkshire United Kingdom BD20 6TD
198 Pfizer Investigational Site London United Kingdom NW1 2PG
199 Pfizer Investigational Site London United Kingdom NW3 2QG
200 Pfizer Investigational Site Peterborough United Kingdom PE3 6DA
201 Pfizer Investigational Site Rhyl, Denbigshire United Kingdom LL18 5UJ
202 Pfizer Investigational Site Sheffield United Kingdom S10 2SJ
203 Pfizer Investigational Site Southampton United Kingdom SO16 6YD
204 Pfizer Investigational Site Yeovil, Somerset United Kingdom BA21 4AT

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00457392
Other Study ID Numbers:
  • A6181087
  • SUN1087
First Posted:
Apr 6, 2007
Last Update Posted:
Oct 29, 2013
Last Verified:
Sep 1, 2013
Keywords provided by Pfizer
Non-small cell lung cancer
sunitinib
erlotinib
Phase 3
Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Erlotinib Hydrochloride
Sunitinib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
Period Title: Overall Study
STARTED 480 480
Treated 473 477
COMPLETED 0 0
NOT COMPLETED 480 480

Baseline Characteristics

Arm/Group Title Sunitinib + Erlotinib Erlotinib Total
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily. Total of all reporting groups
Overall Participants 480 480 960
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
61.10
(9.97)
60.80
(9.13)
60.90
(9.56)
Sex: Female, Male (Count of Participants)
Female
183
38.1%
196
40.8%
379
39.5%
Male
297
61.9%
284
59.2%
581
60.5%

Outcome Measures

1. Primary Outcome
Title Overall Survival (OS)
Description Overall survival is the duration from assignment to study medication to death. For participants who are alive, overall survival is censored at the last contact.
Time Frame Baseline to death or 28 days after last dose for the last participant

Outcome Measure Data

Analysis Population Description
The Full Analysis (FA) set included all participants who were randomized, with study drug assignment designated according to actual randomization, regardless of whether participants received study drug according to the randomization schedule, or received a different drug from that to which they were randomized.
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
Measure Participants 480 480
Median (95% Confidence Interval) [Months]
9.0
8.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Erlotinib, Erlotinib
Comments Differences in OS between treatment arms was analyzed by the 1-sided log rank test, stratified for smoking status (ever versus never), prior bevacizumab therapy (yes versus no) and epidermal growth factor receptor (EGFR) status (positive, versus negative, versus unknown).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1933
Comments p-value was not adjusted for multiple comparisons.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.942
Confidence Interval (2-Sided) 95%
0.822 to 1.079
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Progression-Free Survival (PFS)
Description Time in weeks from assignment to study medication to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame Baseline to disease progression or death due to any cause or 28 days after last dose

Outcome Measure Data

Analysis Population Description
The FA set included all participants who were randomized, with study drug assignment designated according to actual randomization, regardless of whether participants received study drug according to the randomization schedule, or received a different drug from that to which they were randomized.
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
Measure Participants 480 480
Median (95% Confidence Interval) [Weeks]
15.5
8.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Erlotinib, Erlotinib
Comments Differences in PFS between treatment arms was analyzed by the 1-sided log rank test, stratified for smoking status (ever versus never), prior bevacizumab therapy (yes versus no) and EGFR status (positive, versus negative, versus unknown).
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0023
Comments No p-value is adjusted for multiple comparisons for PFS.
Method Log Rank
Comments One-sided log-rank test with alpha=0.025 was used.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.807
Confidence Interval (2-Sided) 95%
0.695 to 0.937
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Percentage of Participants With Objective Response (OR)
Description Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.
Time Frame Baseline to disease progression or discontinuation from study or 28 days after last dose

Outcome Measure Data

Analysis Population Description
The FA set included all participants who were randomized, with study drug assignment designated according to actual randomization, regardless of whether participants received study drug according to the randomization schedule, or received a different drug from that to which they were randomized.
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
Measure Participants 480 480
Number (95% Confidence Interval) [Percentage of participants]
10.60
2.2%
6.90
1.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Erlotinib, Erlotinib
Comments The Cochran-Mantel-Haenszel (CMH) test stratified for smoking status (ever versus never), prior bevacizumab therapy (yes versus no) and EGFR status (positive, versus negative, versus unknown) was used to compare ORR between the 2 treatment arms. The relative risk ratio estimator was used to contrast the treatment effects on response rates. A point estimate of relative risk ratio and 2-sided 95% CI was calculated.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0471
Comments
Method Cochran-Mantel-Haenszel
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.514
Confidence Interval (2-Sided) 95%
1.002 to 2.289
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Duration of Response (DR)
Description Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7.
Time Frame Baseline to disease progression or death or discontinuation from study or 28 days after last dose

Outcome Measure Data

Analysis Population Description
DR was calculated for the subgroup of participants from the FA set, with a confirmed objective tumor response.
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
Measure Participants 51 33
Median (95% Confidence Interval) [Weeks]
39.6
32.3
5. Secondary Outcome
Title One-year Survival Probability
Description The 1 year survival probability was defined as the probability of survival at one year after the date of the start of the study treatment based on the Kaplan Meier estimate.
Time Frame Baseline until death or until 28 days after last dose for the last participant

Outcome Measure Data

Analysis Population Description
The FA set included all participants who were randomized, with study drug assignment designated according to actual randomization, regardless of whether participants received study drug according to the randomization schedule, or received a different drug from that to which they were randomized.
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
Measure Participants 480 480
Number (95% Confidence Interval) [Percent chance of survival]
40.0
37.0
6. Secondary Outcome
Title EuroQol 5-Dimension Questionnaire (EQ-5D)- Health State Profile Utility Score
Description EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates better health state.
Time Frame Baseline and End of Treatment (EOT) or Withdrawal

Outcome Measure Data

Analysis Population Description
Patients Reported Outcome (PRO) Analysis Set included participants from the FA population who had at least one EQ-5D assessment while on treatment. The 'n' signifies those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
Measure Participants 451 465
Baseline
0.750
(0.239)
0.716
(0.263)
End of Treatment (n= 285, 301)
0.615
(0.348)
0.598
(0.339)

Adverse Events

Time Frame
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title Sunitinib + Erlotinib Erlotinib
Arm/Group Description Sunitinib capsule administered orally at a dose of 37.5 milligram (mg) daily (continuous regimen) in a 4 week cycle. Erlotinib administered orally at a dose of 150 mg daily. Placebo capsule matched to sunitinib administered orally daily (continuous regimen) in a 4 week cycle. Erlotinib 150 mg tablet orally daily.
All Cause Mortality
Sunitinib + Erlotinib Erlotinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Sunitinib + Erlotinib Erlotinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 207/473 (43.8%) 181/477 (37.9%)
Blood and lymphatic system disorders
Anaemia 3/473 (0.6%) 5/477 (1%)
Anaemia of malignant disease 1/473 (0.2%) 0/477 (0%)
Febrile neutropenia 1/473 (0.2%) 0/477 (0%)
Neutropenia 0/473 (0%) 1/477 (0.2%)
Thrombocytopenia 2/473 (0.4%) 0/477 (0%)
Cardiac disorders
Acute myocardial infarction 0/473 (0%) 1/477 (0.2%)
Atrioventricular block complete 1/473 (0.2%) 0/477 (0%)
Bundle branch block left 1/473 (0.2%) 0/477 (0%)
Cardiac arrest 0/473 (0%) 1/477 (0.2%)
Cardiac failure 2/473 (0.4%) 3/477 (0.6%)
Cardiac failure congestive 1/473 (0.2%) 0/477 (0%)
Cardiopulmonary failure 1/473 (0.2%) 0/477 (0%)
Cardiovascular insufficiency 1/473 (0.2%) 0/477 (0%)
Coronary artery disease 1/473 (0.2%) 0/477 (0%)
Left ventricular failure 0/473 (0%) 1/477 (0.2%)
Myocardial infarction 3/473 (0.6%) 0/477 (0%)
Pericardial effusion 3/473 (0.6%) 1/477 (0.2%)
Tachyarrhythmia 0/473 (0%) 2/477 (0.4%)
Tachycardia 1/473 (0.2%) 0/477 (0%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula 1/473 (0.2%) 0/477 (0%)
Gastrointestinal disorders
Abdominal pain 1/473 (0.2%) 3/477 (0.6%)
Abdominal pain upper 1/473 (0.2%) 1/477 (0.2%)
Acute abdomen 0/473 (0%) 1/477 (0.2%)
Anal haemorrhage 1/473 (0.2%) 0/477 (0%)
Ascites 1/473 (0.2%) 0/477 (0%)
Constipation 1/473 (0.2%) 1/477 (0.2%)
Diarrhoea 22/473 (4.7%) 5/477 (1%)
Dysphagia 1/473 (0.2%) 0/477 (0%)
Gastric haemorrhage 2/473 (0.4%) 0/477 (0%)
Gastric perforation 0/473 (0%) 1/477 (0.2%)
Gastric ulcer haemorrhage 0/473 (0%) 1/477 (0.2%)
Gastritis 1/473 (0.2%) 0/477 (0%)
Gastrointestinal haemorrhage 2/473 (0.4%) 0/477 (0%)
Gastrointestinal pain 0/473 (0%) 1/477 (0.2%)
Haematemesis 2/473 (0.4%) 1/477 (0.2%)
Ileus paralytic 0/473 (0%) 1/477 (0.2%)
Lower gastrointestinal haemorrhage 1/473 (0.2%) 0/477 (0%)
Nausea 7/473 (1.5%) 5/477 (1%)
Pancreatitis 1/473 (0.2%) 0/477 (0%)
Peritonitis 1/473 (0.2%) 0/477 (0%)
Rectal haemorrhage 1/473 (0.2%) 0/477 (0%)
Small intestinal obstruction 0/473 (0%) 1/477 (0.2%)
Small intestinal perforation 1/473 (0.2%) 0/477 (0%)
Thrombosis mesenteric vessel 0/473 (0%) 1/477 (0.2%)
Vomiting 11/473 (2.3%) 8/477 (1.7%)
General disorders
Asthenia 11/473 (2.3%) 4/477 (0.8%)
Chest pain 0/473 (0%) 4/477 (0.8%)
Death 2/473 (0.4%) 4/477 (0.8%)
Disease progression 70/473 (14.8%) 61/477 (12.8%)
Euthanasia 0/473 (0%) 1/477 (0.2%)
Fatigue 5/473 (1.1%) 1/477 (0.2%)
General physical health deterioration 6/473 (1.3%) 3/477 (0.6%)
Irritability 1/473 (0.2%) 0/477 (0%)
Malaise 1/473 (0.2%) 0/477 (0%)
Mucosal inflammation 1/473 (0.2%) 1/477 (0.2%)
Oedema peripheral 1/473 (0.2%) 1/477 (0.2%)
Pyrexia 6/473 (1.3%) 4/477 (0.8%)
Sudden death 0/473 (0%) 1/477 (0.2%)
Hepatobiliary disorders
Bile duct stone 0/473 (0%) 1/477 (0.2%)
Cholecystitis 2/473 (0.4%) 0/477 (0%)
Cholelithiasis 1/473 (0.2%) 1/477 (0.2%)
Gallbladder perforation 1/473 (0.2%) 0/477 (0%)
Hepatic failure 0/473 (0%) 1/477 (0.2%)
Hepatic function abnormal 2/473 (0.4%) 0/477 (0%)
Hyperbilirubinaemia 1/473 (0.2%) 0/477 (0%)
Immune system disorders
Anaphylactic shock 0/473 (0%) 1/477 (0.2%)
Infections and infestations
Acute tonsillitis 0/473 (0%) 1/477 (0.2%)
Bronchitis 1/473 (0.2%) 1/477 (0.2%)
Bronchopneumonia 2/473 (0.4%) 0/477 (0%)
Clostridial infection 0/473 (0%) 1/477 (0.2%)
Clostridium difficile colitis 1/473 (0.2%) 0/477 (0%)
Device related infection 1/473 (0.2%) 0/477 (0%)
Empyema 1/473 (0.2%) 0/477 (0%)
Endocarditis 1/473 (0.2%) 0/477 (0%)
Erysipelas 1/473 (0.2%) 1/477 (0.2%)
Gastroenteritis 3/473 (0.6%) 1/477 (0.2%)
Hepatitis B 1/473 (0.2%) 0/477 (0%)
Herpes simplex 1/473 (0.2%) 0/477 (0%)
Herpes virus infection 1/473 (0.2%) 0/477 (0%)
Infection 2/473 (0.4%) 1/477 (0.2%)
Influenza 0/473 (0%) 1/477 (0.2%)
Lower respiratory tract infection 0/473 (0%) 1/477 (0.2%)
Lung abscess 1/473 (0.2%) 0/477 (0%)
Lung infection 0/473 (0%) 2/477 (0.4%)
Pneumonia 7/473 (1.5%) 13/477 (2.7%)
Pseudomembranous colitis 0/473 (0%) 1/477 (0.2%)
Pyonephrosis 0/473 (0%) 1/477 (0.2%)
Pyothorax 0/473 (0%) 1/477 (0.2%)
Respiratory tract infection 4/473 (0.8%) 0/477 (0%)
Sepsis 2/473 (0.4%) 1/477 (0.2%)
Septic shock 0/473 (0%) 1/477 (0.2%)
Streptococcal bacteraemia 1/473 (0.2%) 0/477 (0%)
Streptococcal sepsis 1/473 (0.2%) 0/477 (0%)
Urinary tract infection 4/473 (0.8%) 1/477 (0.2%)
Injury, poisoning and procedural complications
Accidental overdose 0/473 (0%) 1/477 (0.2%)
Ankle fracture 0/473 (0%) 1/477 (0.2%)
Fall 0/473 (0%) 1/477 (0.2%)
Hip fracture 0/473 (0%) 1/477 (0.2%)
Joint dislocation 0/473 (0%) 1/477 (0.2%)
Pelvic fracture 1/473 (0.2%) 0/477 (0%)
Road traffic accident 0/473 (0%) 1/477 (0.2%)
Spinal fracture 0/473 (0%) 1/477 (0.2%)
Subdural haemorrhage 0/473 (0%) 1/477 (0.2%)
Upper limb fracture 1/473 (0.2%) 0/477 (0%)
Investigations
Alanine aminotransferase increased 0/473 (0%) 2/477 (0.4%)
Aspartate aminotransferase increased 0/473 (0%) 1/477 (0.2%)
Blood bilirubin increased 1/473 (0.2%) 1/477 (0.2%)
Body temperature increased 1/473 (0.2%) 0/477 (0%)
General physical condition abnormal 1/473 (0.2%) 0/477 (0%)
Haemoglobin decreased 2/473 (0.4%) 1/477 (0.2%)
Hepatic enzyme increased 1/473 (0.2%) 0/477 (0%)
Metabolism and nutrition disorders
Decreased appetite 2/473 (0.4%) 4/477 (0.8%)
Dehydration 9/473 (1.9%) 5/477 (1%)
Hyperglycaemia 1/473 (0.2%) 0/477 (0%)
Hyperkalaemia 1/473 (0.2%) 0/477 (0%)
Hypocalcaemia 2/473 (0.4%) 0/477 (0%)
Hypokalaemia 2/473 (0.4%) 1/477 (0.2%)
Hypomagnesaemia 1/473 (0.2%) 2/477 (0.4%)
Hyponatraemia 1/473 (0.2%) 1/477 (0.2%)
Hypophagia 1/473 (0.2%) 0/477 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/473 (0%) 1/477 (0.2%)
Back pain 1/473 (0.2%) 4/477 (0.8%)
Flank pain 0/473 (0%) 1/477 (0.2%)
Muscle haemorrhage 1/473 (0.2%) 0/477 (0%)
Muscular weakness 1/473 (0.2%) 0/477 (0%)
Musculoskeletal chest pain 1/473 (0.2%) 0/477 (0%)
Musculoskeletal pain 1/473 (0.2%) 0/477 (0%)
Neck pain 1/473 (0.2%) 0/477 (0%)
Osteonecrosis of jaw 1/473 (0.2%) 0/477 (0%)
Pain in extremity 2/473 (0.4%) 0/477 (0%)
Pathological fracture 1/473 (0.2%) 0/477 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liposarcoma 0/473 (0%) 1/477 (0.2%)
Rectal cancer 0/473 (0%) 1/477 (0.2%)
Tumour haemorrhage 1/473 (0.2%) 0/477 (0%)
Tumour pain 1/473 (0.2%) 1/477 (0.2%)
Nervous system disorders
Ataxia 0/473 (0%) 1/477 (0.2%)
Cerebral infarction 2/473 (0.4%) 0/477 (0%)
Cerebral ischaemia 1/473 (0.2%) 0/477 (0%)
Cerebrovascular accident 3/473 (0.6%) 1/477 (0.2%)
Depressed level of consciousness 0/473 (0%) 1/477 (0.2%)
Haemorrhagic stroke 1/473 (0.2%) 0/477 (0%)
Hemiparesis 1/473 (0.2%) 0/477 (0%)
Hemiplegia 0/473 (0%) 1/477 (0.2%)
Ischaemic stroke 1/473 (0.2%) 0/477 (0%)
Lethargy 1/473 (0.2%) 0/477 (0%)
Loss of consciousness 1/473 (0.2%) 0/477 (0%)
Meningorrhagia 1/473 (0.2%) 0/477 (0%)
Monoparesis 0/473 (0%) 1/477 (0.2%)
Neuralgia 0/473 (0%) 1/477 (0.2%)
Neurological decompensation 0/473 (0%) 1/477 (0.2%)
Paralysis 0/473 (0%) 1/477 (0.2%)
Syncope 1/473 (0.2%) 1/477 (0.2%)
Psychiatric disorders
Aggression 1/473 (0.2%) 0/477 (0%)
Anxiety 0/473 (0%) 1/477 (0.2%)
Completed suicide 1/473 (0.2%) 0/477 (0%)
Confusional state 3/473 (0.6%) 2/477 (0.4%)
Mental status changes 1/473 (0.2%) 0/477 (0%)
Psychotic disorder 0/473 (0%) 1/477 (0.2%)
Sopor 0/473 (0%) 1/477 (0.2%)
Suicide attempt 0/473 (0%) 1/477 (0.2%)
Renal and urinary disorders
Anuria 1/473 (0.2%) 0/477 (0%)
Calculus ureteric 0/473 (0%) 1/477 (0.2%)
Focal segmental glomerulosclerosis 1/473 (0.2%) 0/477 (0%)
Haematuria 1/473 (0.2%) 0/477 (0%)
Nephrolithiasis 1/473 (0.2%) 0/477 (0%)
Renal failure 4/473 (0.8%) 1/477 (0.2%)
Renal failure acute 1/473 (0.2%) 1/477 (0.2%)
Urinary retention 0/473 (0%) 1/477 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome 0/473 (0%) 1/477 (0.2%)
Asphyxia 0/473 (0%) 1/477 (0.2%)
Atelectasis 0/473 (0%) 1/477 (0.2%)
Chronic obstructive pulmonary disease 2/473 (0.4%) 2/477 (0.4%)
Cough 0/473 (0%) 1/477 (0.2%)
Dyspnoea 17/473 (3.6%) 21/477 (4.4%)
Epistaxis 3/473 (0.6%) 0/477 (0%)
Haemoptysis 5/473 (1.1%) 4/477 (0.8%)
Hydrothorax 1/473 (0.2%) 0/477 (0%)
Interstitial lung disease 1/473 (0.2%) 1/477 (0.2%)
Lung disorder 0/473 (0%) 2/477 (0.4%)
Lung infiltration 1/473 (0.2%) 0/477 (0%)
Pleural effusion 5/473 (1.1%) 4/477 (0.8%)
Pneumonia aspiration 1/473 (0.2%) 1/477 (0.2%)
Pneumothorax 3/473 (0.6%) 2/477 (0.4%)
Pulmonary embolism 4/473 (0.8%) 7/477 (1.5%)
Pulmonary haemorrhage 1/473 (0.2%) 3/477 (0.6%)
Pulmonary infarction 1/473 (0.2%) 0/477 (0%)
Pulmonary oedema 1/473 (0.2%) 0/477 (0%)
Respiratory arrest 1/473 (0.2%) 0/477 (0%)
Respiratory disorder 0/473 (0%) 1/477 (0.2%)
Respiratory failure 5/473 (1.1%) 12/477 (2.5%)
Respiratory tract congestion 0/473 (0%) 1/477 (0.2%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform 1/473 (0.2%) 0/477 (0%)
Palmar-plantar erythrodysaesthesia syndrome 1/473 (0.2%) 0/477 (0%)
Petechiae 0/473 (0%) 1/477 (0.2%)
Rash 3/473 (0.6%) 0/477 (0%)
Rash generalised 1/473 (0.2%) 0/477 (0%)
Vascular disorders
Aortic aneurysm rupture 1/473 (0.2%) 0/477 (0%)
Circulatory collapse 1/473 (0.2%) 1/477 (0.2%)
Deep vein thrombosis 3/473 (0.6%) 2/477 (0.4%)
Embolism 1/473 (0.2%) 0/477 (0%)
Hypertension 1/473 (0.2%) 1/477 (0.2%)
Hypovolaemic shock 0/473 (0%) 1/477 (0.2%)
Peripheral ischaemia 0/473 (0%) 1/477 (0.2%)
Peripheral vascular disorder 1/473 (0.2%) 0/477 (0%)
Phlebitis 1/473 (0.2%) 0/477 (0%)
Superior vena caval occlusion 0/473 (0%) 1/477 (0.2%)
Other (Not Including Serious) Adverse Events
Sunitinib + Erlotinib Erlotinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 463/473 (97.9%) 461/477 (96.6%)
Blood and lymphatic system disorders
Anaemia 51/473 (10.8%) 23/477 (4.8%)
Anaemia megaloblastic 1/473 (0.2%) 0/477 (0%)
Febrile neutropenia 1/473 (0.2%) 0/477 (0%)
Granulocytopenia 2/473 (0.4%) 0/477 (0%)
Haemorrhagic diathesis 1/473 (0.2%) 0/477 (0%)
Leukocytosis 0/473 (0%) 2/477 (0.4%)
Leukopenia 20/473 (4.2%) 3/477 (0.6%)
Lymph node pain 0/473 (0%) 1/477 (0.2%)
Lymphadenopathy 2/473 (0.4%) 0/477 (0%)
Lymphopenia 9/473 (1.9%) 1/477 (0.2%)
Macrocytosis 0/473 (0%) 1/477 (0.2%)
Neutropenia 34/473 (7.2%) 4/477 (0.8%)
Neutrophilia 0/473 (0%) 1/477 (0.2%)
Thrombocytopenia 32/473 (6.8%) 2/477 (0.4%)
Cardiac disorders
Angina pectoris 1/473 (0.2%) 2/477 (0.4%)
Aortic valve incompetence 1/473 (0.2%) 0/477 (0%)
Arrhythmia 0/473 (0%) 1/477 (0.2%)
Atrial fibrillation 2/473 (0.4%) 4/477 (0.8%)
Atrial flutter 1/473 (0.2%) 0/477 (0%)
Atrioventricular block second degree 1/473 (0.2%) 0/477 (0%)
Bundle branch block left 0/473 (0%) 1/477 (0.2%)
Bundle branch block right 1/473 (0.2%) 1/477 (0.2%)
Cardiac arrest 0/473 (0%) 1/477 (0.2%)
Cardiac failure 3/473 (0.6%) 0/477 (0%)
Extrasystoles 2/473 (0.4%) 0/477 (0%)
Myocardial ischaemia 3/473 (0.6%) 0/477 (0%)
Palpitations 2/473 (0.4%) 2/477 (0.4%)
Pericardial effusion 5/473 (1.1%) 3/477 (0.6%)
Sinus tachycardia 0/473 (0%) 2/477 (0.4%)
Supraventricular extrasystoles 0/473 (0%) 1/477 (0.2%)
Tachycardia 3/473 (0.6%) 6/477 (1.3%)
Ventricular arrhythmia 1/473 (0.2%) 0/477 (0%)
Ventricular extrasystoles 1/473 (0.2%) 3/477 (0.6%)
Congenital, familial and genetic disorders
Trichomegaly 1/473 (0.2%) 0/477 (0%)
Ear and labyrinth disorders
Deafness 1/473 (0.2%) 0/477 (0%)
Dysacusis 1/473 (0.2%) 0/477 (0%)
Ear haemorrhage 1/473 (0.2%) 0/477 (0%)
Ear pain 1/473 (0.2%) 2/477 (0.4%)
Ear pruritus 0/473 (0%) 1/477 (0.2%)
Motion sickness 1/473 (0.2%) 0/477 (0%)
Tinnitus 1/473 (0.2%) 2/477 (0.4%)
Vertigo 6/473 (1.3%) 9/477 (1.9%)
Vertigo positional 1/473 (0.2%) 0/477 (0%)
Endocrine disorders
Adrenal disorder 1/473 (0.2%) 0/477 (0%)
Hyperthyroidism 1/473 (0.2%) 1/477 (0.2%)
Hypothyroidism 2/473 (0.4%) 2/477 (0.4%)
Parathyroid haemorrhage 0/473 (0%) 1/477 (0.2%)
Eye disorders
Blepharitis 1/473 (0.2%) 2/477 (0.4%)
Cataract 0/473 (0%) 1/477 (0.2%)
Conjunctival haemorrhage 1/473 (0.2%) 2/477 (0.4%)
Conjunctivitis 19/473 (4%) 20/477 (4.2%)
Conjunctivitis allergic 0/473 (0%) 1/477 (0.2%)
Diplopia 1/473 (0.2%) 0/477 (0%)
Dry eye 7/473 (1.5%) 9/477 (1.9%)
Erythema of eyelid 0/473 (0%) 1/477 (0.2%)
Eye allergy 1/473 (0.2%) 0/477 (0%)
Eye disorder 1/473 (0.2%) 1/477 (0.2%)
Eye irritation 2/473 (0.4%) 3/477 (0.6%)
Eye oedema 2/473 (0.4%) 0/477 (0%)
Eye pain 0/473 (0%) 2/477 (0.4%)
Eye pruritus 3/473 (0.6%) 4/477 (0.8%)
Eyelid disorder 0/473 (0%) 1/477 (0.2%)
Eyelid function disorder 1/473 (0.2%) 0/477 (0%)
Eyelid oedema 6/473 (1.3%) 1/477 (0.2%)
Eyelid pain 1/473 (0.2%) 0/477 (0%)
Keratitis 3/473 (0.6%) 0/477 (0%)
Keratoconjunctivitis sicca 2/473 (0.4%) 0/477 (0%)
Lacrimal gland enlargement 1/473 (0.2%) 0/477 (0%)
Lacrimation increased 8/473 (1.7%) 3/477 (0.6%)
Lenticular opacities 0/473 (0%) 1/477 (0.2%)
Mydriasis 1/473 (0.2%) 0/477 (0%)
Ocular hyperaemia 1/473 (0.2%) 1/477 (0.2%)
Ocular icterus 2/473 (0.4%) 0/477 (0%)
Ocular surface disease 0/473 (0%) 1/477 (0.2%)
Panophthalmitis 1/473 (0.2%) 0/477 (0%)
Ulcerative keratitis 1/473 (0.2%) 0/477 (0%)
Vision blurred 5/473 (1.1%) 5/477 (1%)
Visual acuity reduced 2/473 (0.4%) 0/477 (0%)
Vitreous floaters 1/473 (0.2%) 1/477 (0.2%)
Gastrointestinal disorders
Abdominal discomfort 2/473 (0.4%) 1/477 (0.2%)
Abdominal distension 7/473 (1.5%) 4/477 (0.8%)
Abdominal pain 30/473 (6.3%) 24/477 (5%)
Abdominal pain lower 0/473 (0%) 1/477 (0.2%)
Abdominal pain upper 15/473 (3.2%) 22/477 (4.6%)
Abdominal strangulated hernia 1/473 (0.2%) 0/477 (0%)
Abnormal faeces 0/473 (0%) 1/477 (0.2%)
Anal haemorrhage 1/473 (0.2%) 0/477 (0%)
Anorectal discomfort 1/473 (0.2%) 0/477 (0%)
Aphagia 0/473 (0%) 1/477 (0.2%)
Aphthous stomatitis 5/473 (1.1%) 2/477 (0.4%)
Aptyalism 1/473 (0.2%) 0/477 (0%)
Ascites 5/473 (1.1%) 2/477 (0.4%)
Breath odour 1/473 (0.2%) 0/477 (0%)
Chapped lips 0/473 (0%) 1/477 (0.2%)
Cheilitis 0/473 (0%) 4/477 (0.8%)
Colitis 1/473 (0.2%) 1/477 (0.2%)
Colitis ischaemic 0/473 (0%) 1/477 (0.2%)
Constipation 29/473 (6.1%) 42/477 (8.8%)
Dental caries 0/473 (0%) 1/477 (0.2%)
Diarrhoea 335/473 (70.8%) 188/477 (39.4%)
Diarrhoea haemorrhagic 1/473 (0.2%) 0/477 (0%)
Dry mouth 11/473 (2.3%) 15/477 (3.1%)
Duodenitis 1/473 (0.2%) 0/477 (0%)
Dyspepsia 41/473 (8.7%) 34/477 (7.1%)
Dysphagia 10/473 (2.1%) 6/477 (1.3%)
Enteritis 0/473 (0%) 1/477 (0.2%)
Epigastric discomfort 1/473 (0.2%) 0/477 (0%)
Erosive duodenitis 0/473 (0%) 1/477 (0.2%)
Erosive oesophagitis 1/473 (0.2%) 0/477 (0%)
Eructation 2/473 (0.4%) 0/477 (0%)
Flatulence 7/473 (1.5%) 8/477 (1.7%)
Frequent bowel movements 1/473 (0.2%) 0/477 (0%)
Gastric haemorrhage 1/473 (0.2%) 0/477 (0%)
Gastric ulcer 0/473 (0%) 1/477 (0.2%)
Gastritis 8/473 (1.7%) 1/477 (0.2%)
Gastritis atrophic 0/473 (0%) 1/477 (0.2%)
Gastrointestinal hypermotility 0/473 (0%) 1/477 (0.2%)
Gastrointestinal motility disorder 0/473 (0%) 1/477 (0.2%)
Gastrointestinal sounds abnormal 0/473 (0%) 1/477 (0.2%)
Gastrooesophageal reflux disease 5/473 (1.1%) 6/477 (1.3%)
Gingival bleeding 6/473 (1.3%) 3/477 (0.6%)
Gingivitis 3/473 (0.6%) 0/477 (0%)
Glossitis 1/473 (0.2%) 1/477 (0.2%)
Glossodynia 6/473 (1.3%) 4/477 (0.8%)
Haematemesis 1/473 (0.2%) 1/477 (0.2%)
Haematochezia 7/473 (1.5%) 0/477 (0%)
Haemorrhoidal haemorrhage 1/473 (0.2%) 2/477 (0.4%)
Haemorrhoids 6/473 (1.3%) 3/477 (0.6%)
Hiatus hernia 1/473 (0.2%) 1/477 (0.2%)
Hyperchlorhydria 3/473 (0.6%) 0/477 (0%)
Hypoaesthesia oral 1/473 (0.2%) 0/477 (0%)
Impaired gastric emptying 1/473 (0.2%) 0/477 (0%)
Inguinal hernia 0/473 (0%) 1/477 (0.2%)
Jejunitis 1/473 (0.2%) 0/477 (0%)
Lip blister 1/473 (0.2%) 0/477 (0%)
Lip dry 2/473 (0.4%) 1/477 (0.2%)
Lip oedema 1/473 (0.2%) 0/477 (0%)
Lip pain 1/473 (0.2%) 0/477 (0%)
Lip swelling 1/473 (0.2%) 0/477 (0%)
Lip ulceration 0/473 (0%) 1/477 (0.2%)
Lower gastrointestinal haemorrhage 0/473 (0%) 1/477 (0.2%)
Melaena 2/473 (0.4%) 1/477 (0.2%)
Mouth haemorrhage 1/473 (0.2%) 0/477 (0%)
Mouth ulceration 5/473 (1.1%) 3/477 (0.6%)
Nausea 114/473 (24.1%) 90/477 (18.9%)
Odynophagia 1/473 (0.2%) 0/477 (0%)
Oesophageal pain 1/473 (0.2%) 1/477 (0.2%)
Oesophageal stenosis 1/473 (0.2%) 0/477 (0%)
Oesophageal ulcer 0/473 (0%) 1/477 (0.2%)
Oesophagitis 3/473 (0.6%) 3/477 (0.6%)
Oral discomfort 1/473 (0.2%) 0/477 (0%)
Oral pain 5/473 (1.1%) 6/477 (1.3%)
Rectal haemorrhage 9/473 (1.9%) 1/477 (0.2%)
Rectal tenesmus 0/473 (0%) 1/477 (0.2%)
Reflux gastritis 1/473 (0.2%) 0/477 (0%)
Reflux oesophagitis 1/473 (0.2%) 1/477 (0.2%)
Retching 0/473 (0%) 1/477 (0.2%)
Salivary hypersecretion 0/473 (0%) 1/477 (0.2%)
Stomatitis 28/473 (5.9%) 21/477 (4.4%)
Thrombosis mesenteric vessel 0/473 (0%) 1/477 (0.2%)
Tongue haemorrhage 1/473 (0.2%) 0/477 (0%)
Tooth deposit 0/473 (0%) 1/477 (0.2%)
Tooth discolouration 0/473 (0%) 1/477 (0.2%)
Tooth disorder 0/473 (0%) 1/477 (0.2%)
Tooth loss 1/473 (0.2%) 0/477 (0%)
Toothache 1/473 (0.2%) 3/477 (0.6%)
Umbilical hernia 1/473 (0.2%) 0/477 (0%)
Upper gastrointestinal haemorrhage 1/473 (0.2%) 0/477 (0%)
Vomiting 86/473 (18.2%) 66/477 (13.8%)
General disorders
Asthenia 49/473 (10.4%) 50/477 (10.5%)
Axillary pain 0/473 (0%) 2/477 (0.4%)
Catheter site pain 1/473 (0.2%) 1/477 (0.2%)
Chest discomfort 5/473 (1.1%) 1/477 (0.2%)
Chest pain 44/473 (9.3%) 47/477 (9.9%)
Chills 8/473 (1.7%) 6/477 (1.3%)
Condition aggravated 1/473 (0.2%) 0/477 (0%)
Device dislocation 0/473 (0%) 1/477 (0.2%)
Discomfort 1/473 (0.2%) 0/477 (0%)
Disease progression 2/473 (0.4%) 5/477 (1%)
Face oedema 2/473 (0.4%) 0/477 (0%)
Fatigue 128/473 (27.1%) 100/477 (21%)
Feeling abnormal 0/473 (0%) 1/477 (0.2%)
Feeling cold 3/473 (0.6%) 1/477 (0.2%)
Gait disturbance 2/473 (0.4%) 2/477 (0.4%)
General physical health deterioration 3/473 (0.6%) 3/477 (0.6%)
Hyperpyrexia 3/473 (0.6%) 0/477 (0%)
Impaired healing 0/473 (0%) 1/477 (0.2%)
Implant site discharge 1/473 (0.2%) 0/477 (0%)
Influenza like illness 5/473 (1.1%) 2/477 (0.4%)
Malaise 2/473 (0.4%) 2/477 (0.4%)
Medical device complication 1/473 (0.2%) 0/477 (0%)
Mucosal dryness 1/473 (0.2%) 1/477 (0.2%)
Mucosal inflammation 40/473 (8.5%) 27/477 (5.7%)
Mucous membrane disorder 0/473 (0%) 1/477 (0.2%)
Non-cardiac chest pain 3/473 (0.6%) 0/477 (0%)
Oedema 4/473 (0.8%) 6/477 (1.3%)
Oedema peripheral 27/473 (5.7%) 26/477 (5.5%)
Pain 4/473 (0.8%) 10/477 (2.1%)
Performance status decreased 1/473 (0.2%) 0/477 (0%)
Pyrexia 43/473 (9.1%) 37/477 (7.8%)
Sensation of foreign body 0/473 (0%) 1/477 (0.2%)
Ulcer 0/473 (0%) 1/477 (0.2%)
Vestibulitis 0/473 (0%) 1/477 (0.2%)
Xerosis 2/473 (0.4%) 1/477 (0.2%)
Hepatobiliary disorders
Biliary dilatation 1/473 (0.2%) 0/477 (0%)
Cholecystitis 1/473 (0.2%) 0/477 (0%)
Hepatic failure 1/473 (0.2%) 0/477 (0%)
Hepatic function abnormal 3/473 (0.6%) 0/477 (0%)
Hepatic pain 0/473 (0%) 2/477 (0.4%)
Hepatotoxicity 1/473 (0.2%) 3/477 (0.6%)
Hyperbilirubinaemia 23/473 (4.9%) 6/477 (1.3%)
Jaundice 2/473 (0.4%) 0/477 (0%)
Immune system disorders
Drug hypersensitivity 0/473 (0%) 2/477 (0.4%)
Hypersensitivity 0/473 (0%) 1/477 (0.2%)
Infections and infestations
Abdominal wall infection 1/473 (0.2%) 1/477 (0.2%)
Abscess 2/473 (0.4%) 0/477 (0%)
Abscess limb 2/473 (0.4%) 1/477 (0.2%)
Abscess oral 1/473 (0.2%) 0/477 (0%)
Anal abscess 1/473 (0.2%) 0/477 (0%)
Anal fungal infection 1/473 (0.2%) 0/477 (0%)
Arthritis infective 1/473 (0.2%) 0/477 (0%)
Bronchitis 12/473 (2.5%) 14/477 (2.9%)
Bronchopneumonia 1/473 (0.2%) 0/477 (0%)
Candidiasis 4/473 (0.8%) 4/477 (0.8%)
Cellulitis 1/473 (0.2%) 0/477 (0%)
Cystitis 9/473 (1.9%) 5/477 (1%)
Dermatitis infected 1/473 (0.2%) 1/477 (0.2%)
Ear infection 1/473 (0.2%) 2/477 (0.4%)
Erysipelas 2/473 (0.4%) 0/477 (0%)
Eye infection 1/473 (0.2%) 1/477 (0.2%)
Folliculitis 6/473 (1.3%) 7/477 (1.5%)
Fungal infection 0/473 (0%) 2/477 (0.4%)
Fungal skin infection 0/473 (0%) 7/477 (1.5%)
Furuncle 0/473 (0%) 1/477 (0.2%)
Gastroenteritis 0/473 (0%) 3/477 (0.6%)
H1N1 influenza 0/473 (0%) 1/477 (0.2%)
Herpes virus infection 1/473 (0.2%) 0/477 (0%)
Herpes zoster 3/473 (0.6%) 3/477 (0.6%)
Infected skin ulcer 1/473 (0.2%) 0/477 (0%)
Infection 4/473 (0.8%) 4/477 (0.8%)
Influenza 7/473 (1.5%) 13/477 (2.7%)
Labyrinthitis 2/473 (0.4%) 1/477 (0.2%)
Localised infection 7/473 (1.5%) 3/477 (0.6%)
Lower respiratory tract infection 9/473 (1.9%) 10/477 (2.1%)
Lung infection 1/473 (0.2%) 3/477 (0.6%)
Lymphangitis 0/473 (0%) 1/477 (0.2%)
Nail infection 2/473 (0.4%) 3/477 (0.6%)
Nasopharyngitis 9/473 (1.9%) 14/477 (2.9%)
Onychomycosis 0/473 (0%) 1/477 (0.2%)
Oral candidiasis 9/473 (1.9%) 3/477 (0.6%)
Oral fungal infection 1/473 (0.2%) 5/477 (1%)
Oral herpes 2/473 (0.4%) 0/477 (0%)
Oral infection 1/473 (0.2%) 0/477 (0%)
Otitis externa 0/473 (0%) 2/477 (0.4%)
Otitis media 1/473 (0.2%) 1/477 (0.2%)
Parainfluenzae virus infection 0/473 (0%) 1/477 (0.2%)
Paronychia 25/473 (5.3%) 19/477 (4%)
Pharyngitis 5/473 (1.1%) 4/477 (0.8%)
Pneumonia 14/473 (3%) 17/477 (3.6%)
Pulpitis dental 1/473 (0.2%) 0/477 (0%)
Pyothorax 1/473 (0.2%) 0/477 (0%)
Rash pustular 5/473 (1.1%) 3/477 (0.6%)
Respiratory tract infection 7/473 (1.5%) 6/477 (1.3%)
Rhinitis 1/473 (0.2%) 3/477 (0.6%)
Sepsis 0/473 (0%) 1/477 (0.2%)
Sialoadenitis 1/473 (0.2%) 0/477 (0%)
Sinusitis 3/473 (0.6%) 2/477 (0.4%)
Skin bacterial infection 1/473 (0.2%) 0/477 (0%)
Skin infection 1/473 (0.2%) 3/477 (0.6%)
Soft tissue infection 1/473 (0.2%) 0/477 (0%)
Staphylococcal infection 1/473 (0.2%) 2/477 (0.4%)
Subcutaneous abscess 0/473 (0%) 1/477 (0.2%)
Tinea cruris 0/473 (0%) 1/477 (0.2%)
Tinea pedis 1/473 (0.2%) 3/477 (0.6%)
Tonsillitis 1/473 (0.2%) 1/477 (0.2%)
Tooth abscess 1/473 (0.2%) 1/477 (0.2%)
Tooth infection 2/473 (0.4%) 0/477 (0%)
Tracheitis 0/473 (0%) 2/477 (0.4%)
Upper respiratory tract infection 8/473 (1.7%) 12/477 (2.5%)
Urinary tract infection 13/473 (2.7%) 15/477 (3.1%)
Vaginal infection 0/473 (0%) 2/477 (0.4%)
Viral infection 1/473 (0.2%) 2/477 (0.4%)
Wound infection 1/473 (0.2%) 0/477 (0%)
Injury, poisoning and procedural complications
Accidental overdose 1/473 (0.2%) 0/477 (0%)
Clavicle fracture 0/473 (0%) 1/477 (0.2%)
Contusion 1/473 (0.2%) 0/477 (0%)
Excoriation 2/473 (0.4%) 0/477 (0%)
Fall 1/473 (0.2%) 1/477 (0.2%)
Foot fracture 0/473 (0%) 1/477 (0.2%)
Humerus fracture 0/473 (0%) 1/477 (0.2%)
Inappropriate schedule of drug administration 1/473 (0.2%) 0/477 (0%)
Joint dislocation 1/473 (0.2%) 0/477 (0%)
Joint injury 0/473 (0%) 1/477 (0.2%)
Medication error 1/473 (0.2%) 2/477 (0.4%)
Overdose 2/473 (0.4%) 1/477 (0.2%)
Periorbital haematoma 1/473 (0.2%) 0/477 (0%)
Postoperative wound complication 1/473 (0.2%) 0/477 (0%)
Procedural nausea 1/473 (0.2%) 0/477 (0%)
Rib fracture 0/473 (0%) 1/477 (0.2%)
Road traffic accident 1/473 (0.2%) 1/477 (0.2%)
Scratch 1/473 (0.2%) 0/477 (0%)
Spinal compression fracture 0/473 (0%) 1/477 (0.2%)
Sternal fracture 1/473 (0.2%) 0/477 (0%)
Sunburn 0/473 (0%) 1/477 (0.2%)
Thermal burn 0/473 (0%) 1/477 (0.2%)
Wound 2/473 (0.4%) 1/477 (0.2%)
Wound haemorrhage 0/473 (0%) 1/477 (0.2%)
Wound secretion 0/473 (0%) 1/477 (0.2%)
Investigations
Alanine aminotransferase increased 13/473 (2.7%) 11/477 (2.3%)
Aspartate aminotransferase increased 12/473 (2.5%) 10/477 (2.1%)
Aspiration bronchial 0/473 (0%) 1/477 (0.2%)
Blood albumin decreased 1/473 (0.2%) 0/477 (0%)
Blood alkaline phosphatase increased 4/473 (0.8%) 10/477 (2.1%)
Blood bilirubin increased 3/473 (0.6%) 1/477 (0.2%)
Blood calcium increased 1/473 (0.2%) 1/477 (0.2%)
Blood creatine increased 1/473 (0.2%) 0/477 (0%)
Blood creatinine increased 6/473 (1.3%) 4/477 (0.8%)
Blood lactate dehydrogenase increased 6/473 (1.3%) 5/477 (1%)
Blood magnesium decreased 2/473 (0.4%) 0/477 (0%)
Blood phosphorus decreased 1/473 (0.2%) 1/477 (0.2%)
Blood potassium decreased 2/473 (0.4%) 1/477 (0.2%)
Blood potassium increased 0/473 (0%) 1/477 (0.2%)
Blood pressure increased 4/473 (0.8%) 2/477 (0.4%)
Blood thyroid stimulating hormone increased 0/473 (0%) 2/477 (0.4%)
Blood urea decreased 1/473 (0.2%) 0/477 (0%)
Blood urea increased 2/473 (0.4%) 2/477 (0.4%)
Blood uric acid decreased 1/473 (0.2%) 0/477 (0%)
Blood uric acid increased 0/473 (0%) 1/477 (0.2%)
Blood urine present 1/473 (0.2%) 2/477 (0.4%)
Body temperature decreased 0/473 (0%) 1/477 (0.2%)
Body temperature increased 2/473 (0.4%) 2/477 (0.4%)
Breath sounds abnormal 4/473 (0.8%) 5/477 (1%)
C-reactive protein increased 4/473 (0.8%) 2/477 (0.4%)
Cardiac murmur 0/473 (0%) 1/477 (0.2%)
Creatinine renal clearance decreased 1/473 (0.2%) 0/477 (0%)
ECG signs of myocardial ischaemia 0/473 (0%) 1/477 (0.2%)
Eastern cooperative oncology group performance status worsened 1/473 (0.2%) 1/477 (0.2%)
Electrocardiogram QT prolonged 1/473 (0.2%) 2/477 (0.4%)
Fibrin D dimer increased 1/473 (0.2%) 0/477 (0%)
Gamma-glutamyltransferase increased 1/473 (0.2%) 1/477 (0.2%)
Haematocrit decreased 1/473 (0.2%) 0/477 (0%)
Haemoglobin decreased 7/473 (1.5%) 8/477 (1.7%)
Heart rate irregular 0/473 (0%) 1/477 (0.2%)
Hepatic enzyme increased 1/473 (0.2%) 0/477 (0%)
Hypophonesis 0/473 (0%) 1/477 (0.2%)
International normalised ratio increased 0/473 (0%) 1/477 (0.2%)
Neutrophil count decreased 2/473 (0.4%) 1/477 (0.2%)
Oxygen saturation decreased 1/473 (0.2%) 0/477 (0%)
Platelet count decreased 6/473 (1.3%) 3/477 (0.6%)
Platelet count increased 0/473 (0%) 1/477 (0.2%)
Protein total decreased 1/473 (0.2%) 1/477 (0.2%)
Renal function test abnormal 0/473 (0%) 1/477 (0.2%)
Thrombin time prolonged 0/473 (0%) 1/477 (0.2%)
Thyroxine increased 1/473 (0.2%) 0/477 (0%)
Transaminases increased 1/473 (0.2%) 0/477 (0%)
Weight decreased 79/473 (16.7%) 64/477 (13.4%)
Weight increased 3/473 (0.6%) 0/477 (0%)
White blood cell count decreased 4/473 (0.8%) 0/477 (0%)
White blood cell count increased 1/473 (0.2%) 1/477 (0.2%)
Metabolism and nutrition disorders
Cachexia 4/473 (0.8%) 1/477 (0.2%)
Decreased appetite 190/473 (40.2%) 133/477 (27.9%)
Dehydration 13/473 (2.7%) 8/477 (1.7%)
Diabetes mellitus 0/473 (0%) 3/477 (0.6%)
Fluid retention 2/473 (0.4%) 1/477 (0.2%)
Food intolerance 0/473 (0%) 1/477 (0.2%)
Gout 0/473 (0%) 1/477 (0.2%)
Hypercalcaemia 5/473 (1.1%) 6/477 (1.3%)
Hypercholesterolaemia 0/473 (0%) 1/477 (0.2%)
Hypercreatininaemia 2/473 (0.4%) 0/477 (0%)
Hyperglycaemia 2/473 (0.4%) 5/477 (1%)
Hyperkalaemia 3/473 (0.6%) 5/477 (1%)
Hypertriglyceridaemia 1/473 (0.2%) 0/477 (0%)
Hyperuricaemia 3/473 (0.6%) 2/477 (0.4%)
Hypoalbuminaemia 2/473 (0.4%) 7/477 (1.5%)
Hypocalcaemia 9/473 (1.9%) 1/477 (0.2%)
Hypoglycaemia 2/473 (0.4%) 0/477 (0%)
Hypokalaemia 33/473 (7%) 13/477 (2.7%)
Hypomagnesaemia 18/473 (3.8%) 10/477 (2.1%)
Hyponatraemia 5/473 (1.1%) 6/477 (1.3%)
Hypophagia 0/473 (0%) 1/477 (0.2%)
Hypophosphataemia 7/473 (1.5%) 4/477 (0.8%)
Malnutrition 0/473 (0%) 2/477 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia 12/473 (2.5%) 17/477 (3.6%)
Arthritis 4/473 (0.8%) 0/477 (0%)
Back pain 29/473 (6.1%) 32/477 (6.7%)
Bone pain 15/473 (3.2%) 14/477 (2.9%)
Bursitis 0/473 (0%) 1/477 (0.2%)
Dupuytren's contracture 0/473 (0%) 1/477 (0.2%)
Fasciitis 1/473 (0.2%) 0/477 (0%)
Finger deformity 0/473 (0%) 1/477 (0.2%)
Fistula 0/473 (0%) 1/477 (0.2%)
Flank pain 0/473 (0%) 3/477 (0.6%)
Groin pain 1/473 (0.2%) 2/477 (0.4%)
Hypercreatinaemia 1/473 (0.2%) 0/477 (0%)
Joint range of motion decreased 1/473 (0.2%) 0/477 (0%)
Joint stiffness 1/473 (0.2%) 1/477 (0.2%)
Joint swelling 1/473 (0.2%) 1/477 (0.2%)
Mobility decreased 1/473 (0.2%) 0/477 (0%)
Muscle atrophy 1/473 (0.2%) 0/477 (0%)
Muscle contracture 0/473 (0%) 1/477 (0.2%)
Muscle disorder 0/473 (0%) 1/477 (0.2%)
Muscle haemorrhage 1/473 (0.2%) 0/477 (0%)
Muscle spasms 10/473 (2.1%) 19/477 (4%)
Muscular weakness 7/473 (1.5%) 7/477 (1.5%)
Musculoskeletal chest pain 8/473 (1.7%) 13/477 (2.7%)
Musculoskeletal disorder 0/473 (0%) 2/477 (0.4%)
Musculoskeletal pain 16/473 (3.4%) 9/477 (1.9%)
Musculoskeletal stiffness 1/473 (0.2%) 1/477 (0.2%)
Myalgia 8/473 (1.7%) 14/477 (2.9%)
Myositis 1/473 (0.2%) 0/477 (0%)
Neck pain 3/473 (0.6%) 7/477 (1.5%)
Osteonecrosis of jaw 1/473 (0.2%) 0/477 (0%)
Pain in extremity 23/473 (4.9%) 26/477 (5.5%)
Pain in jaw 2/473 (0.4%) 0/477 (0%)
Palmar fasciitis 1/473 (0.2%) 0/477 (0%)
Pathological fracture 1/473 (0.2%) 0/477 (0%)
Plantar fasciitis 1/473 (0.2%) 0/477 (0%)
Rotator cuff syndrome 0/473 (0%) 1/477 (0.2%)
Spondylitis 1/473 (0.2%) 1/477 (0.2%)
Synovial cyst 1/473 (0.2%) 0/477 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm 0/473 (0%) 1/477 (0.2%)
Cancer pain 5/473 (1.1%) 0/477 (0%)
Nasal cavity cancer 1/473 (0.2%) 0/477 (0%)
Non-small cell lung cancer 0/473 (0%) 1/477 (0.2%)
Seborrhoeic keratosis 1/473 (0.2%) 0/477 (0%)
Tumour haemorrhage 1/473 (0.2%) 0/477 (0%)
Tumour pain 5/473 (1.1%) 4/477 (0.8%)
Nervous system disorders
Acrodynia 1/473 (0.2%) 0/477 (0%)
Ageusia 10/473 (2.1%) 1/477 (0.2%)
Anosmia 1/473 (0.2%) 0/477 (0%)
Aphasia 0/473 (0%) 1/477 (0.2%)
Areflexia 0/473 (0%) 1/477 (0.2%)
Ataxia 1/473 (0.2%) 0/477 (0%)
Balance disorder 1/473 (0.2%) 2/477 (0.4%)
Burning sensation 0/473 (0%) 1/477 (0.2%)
Cerebral ischaemia 0/473 (0%) 1/477 (0.2%)
Cerebrovascular accident 0/473 (0%) 1/477 (0.2%)
Clonus 1/473 (0.2%) 0/477 (0%)
Convulsion 2/473 (0.4%) 1/477 (0.2%)
Coordination abnormal 1/473 (0.2%) 0/477 (0%)
Depressed level of consciousness 0/473 (0%) 1/477 (0.2%)
Disturbance in attention 0/473 (0%) 1/477 (0.2%)
Dizziness 21/473 (4.4%) 27/477 (5.7%)
Dysaesthesia 1/473 (0.2%) 0/477 (0%)
Dysarthria 4/473 (0.8%) 0/477 (0%)
Dysgeusia 64/473 (13.5%) 27/477 (5.7%)
Dyslalia 1/473 (0.2%) 0/477 (0%)
Epilepsy 1/473 (0.2%) 1/477 (0.2%)
Facial neuralgia 0/473 (0%) 1/477 (0.2%)
Facial paresis 0/473 (0%) 1/477 (0.2%)
Facial spasm 1/473 (0.2%) 0/477 (0%)
Headache 25/473 (5.3%) 23/477 (4.8%)
Horner's syndrome 1/473 (0.2%) 0/477 (0%)
Hyperaesthesia 0/473 (0%) 1/477 (0.2%)
Hypertonia 1/473 (0.2%) 0/477 (0%)
Hypoaesthesia 4/473 (0.8%) 4/477 (0.8%)
Hypogeusia 3/473 (0.6%) 0/477 (0%)
Hypotonia 1/473 (0.2%) 0/477 (0%)
Intracranial aneurysm 0/473 (0%) 1/477 (0.2%)
Lethargy 4/473 (0.8%) 4/477 (0.8%)
Memory impairment 1/473 (0.2%) 1/477 (0.2%)
Monoplegia 1/473 (0.2%) 1/477 (0.2%)
Motor dysfunction 1/473 (0.2%) 1/477 (0.2%)
Muscle contractions involuntary 1/473 (0.2%) 0/477 (0%)
Myoclonus 1/473 (0.2%) 0/477 (0%)
Nervous system disorder 0/473 (0%) 1/477 (0.2%)
Neuralgia 0/473 (0%) 3/477 (0.6%)
Neuropathy peripheral 6/473 (1.3%) 5/477 (1%)
Paraesthesia 7/473 (1.5%) 8/477 (1.7%)
Peripheral motor neuropathy 3/473 (0.6%) 4/477 (0.8%)
Peripheral sensory neuropathy 7/473 (1.5%) 9/477 (1.9%)
Petit mal epilepsy 0/473 (0%) 1/477 (0.2%)
Polyneuropathy 1/473 (0.2%) 6/477 (1.3%)
Presyncope 0/473 (0%) 2/477 (0.4%)
Sciatica 0/473 (0%) 1/477 (0.2%)
Sensory disturbance 0/473 (0%) 1/477 (0.2%)
Somnolence 6/473 (1.3%) 2/477 (0.4%)
Spinal cord compression 1/473 (0.2%) 0/477 (0%)
Syncope 4/473 (0.8%) 4/477 (0.8%)
Transient ischaemic attack 1/473 (0.2%) 0/477 (0%)
Tremor 4/473 (0.8%) 3/477 (0.6%)
Vagus nerve disorder 0/473 (0%) 1/477 (0.2%)
Visual field defect 0/473 (0%) 1/477 (0.2%)
Vocal cord paralysis 1/473 (0.2%) 0/477 (0%)
Psychiatric disorders
Agitation 3/473 (0.6%) 2/477 (0.4%)
Anxiety 19/473 (4%) 17/477 (3.6%)
Confusional state 6/473 (1.3%) 3/477 (0.6%)
Delirium 0/473 (0%) 1/477 (0.2%)
Depressed mood 1/473 (0.2%) 1/477 (0.2%)
Depression 15/473 (3.2%) 15/477 (3.1%)
Hallucination 1/473 (0.2%) 0/477 (0%)
Insomnia 21/473 (4.4%) 28/477 (5.9%)
Listless 0/473 (0%) 1/477 (0.2%)
Mood altered 2/473 (0.4%) 1/477 (0.2%)
Nervousness 0/473 (0%) 1/477 (0.2%)
Nightmare 0/473 (0%) 1/477 (0.2%)
Sleep disorder 1/473 (0.2%) 3/477 (0.6%)
Sopor 0/473 (0%) 1/477 (0.2%)
Stress 0/473 (0%) 1/477 (0.2%)
Suicidal ideation 0/473 (0%) 1/477 (0.2%)
Renal and urinary disorders
Albuminuria 0/473 (0%) 1/477 (0.2%)
Azotaemia 1/473 (0.2%) 0/477 (0%)
Calculus ureteric 2/473 (0.4%) 0/477 (0%)
Calculus urinary 1/473 (0.2%) 0/477 (0%)
Choluria 1/473 (0.2%) 0/477 (0%)
Chromaturia 1/473 (0.2%) 1/477 (0.2%)
Dysuria 9/473 (1.9%) 7/477 (1.5%)
Haematuria 7/473 (1.5%) 4/477 (0.8%)
Haemoglobinuria 1/473 (0.2%) 0/477 (0%)
Micturition urgency 1/473 (0.2%) 0/477 (0%)
Nephrolithiasis 1/473 (0.2%) 0/477 (0%)
Nephrotic syndrome 1/473 (0.2%) 0/477 (0%)
Nocturia 1/473 (0.2%) 1/477 (0.2%)
Pollakiuria 0/473 (0%) 1/477 (0.2%)
Polyuria 0/473 (0%) 1/477 (0.2%)
Proteinuria 21/473 (4.4%) 10/477 (2.1%)
Renal colic 1/473 (0.2%) 0/477 (0%)
Renal cyst 1/473 (0.2%) 0/477 (0%)
Renal failure 1/473 (0.2%) 2/477 (0.4%)
Renal failure acute 2/473 (0.4%) 0/477 (0%)
Renal impairment 0/473 (0%) 1/477 (0.2%)
Renal pain 2/473 (0.4%) 0/477 (0%)
Tubulointerstitial nephritis 1/473 (0.2%) 0/477 (0%)
Urinary incontinence 0/473 (0%) 1/477 (0.2%)
Urinary retention 1/473 (0.2%) 2/477 (0.4%)
Urine flow decreased 0/473 (0%) 1/477 (0.2%)
Reproductive system and breast disorders
Benign prostatic hyperplasia 1/473 (0.2%) 0/477 (0%)
Breast discharge 0/473 (0%) 1/477 (0.2%)
Breast oedema 1/473 (0.2%) 0/477 (0%)
Breast pain 0/473 (0%) 1/477 (0.2%)
Erectile dysfunction 1/473 (0.2%) 0/477 (0%)
Genital rash 2/473 (0.4%) 1/477 (0.2%)
Menstruation irregular 1/473 (0.2%) 1/477 (0.2%)
Pelvic pain 0/473 (0%) 4/477 (0.8%)
Uterine haemorrhage 1/473 (0.2%) 0/477 (0%)
Vaginal discharge 0/473 (0%) 3/477 (0.6%)
Vaginal haemorrhage 1/473 (0.2%) 0/477 (0%)
Vulvovaginal pruritus 0/473 (0%) 1/477 (0.2%)
Respiratory, thoracic and mediastinal disorders
Atelectasis 1/473 (0.2%) 1/477 (0.2%)
Bronchospasm 2/473 (0.4%) 0/477 (0%)
Choking 0/473 (0%) 1/477 (0.2%)
Chronic obstructive pulmonary disease 0/473 (0%) 3/477 (0.6%)
Cough 81/473 (17.1%) 96/477 (20.1%)
Diaphragmalgia 0/473 (0%) 1/477 (0.2%)
Dry throat 1/473 (0.2%) 0/477 (0%)
Dysphonia 13/473 (2.7%) 14/477 (2.9%)
Dyspnoea 95/473 (20.1%) 103/477 (21.6%)
Dyspnoea exertional 7/473 (1.5%) 8/477 (1.7%)
Epistaxis 43/473 (9.1%) 21/477 (4.4%)
Haemoptysis 34/473 (7.2%) 29/477 (6.1%)
Hiccups 3/473 (0.6%) 0/477 (0%)
Hydrothorax 1/473 (0.2%) 0/477 (0%)
Hypoventilation 1/473 (0.2%) 0/477 (0%)
Hypoxia 4/473 (0.8%) 5/477 (1%)
Increased upper airway secretion 1/473 (0.2%) 0/477 (0%)
Interstitial lung disease 1/473 (0.2%) 0/477 (0%)
Lung disorder 0/473 (0%) 1/477 (0.2%)
Lung infiltration 1/473 (0.2%) 0/477 (0%)
Nasal congestion 2/473 (0.4%) 0/477 (0%)
Nasal dryness 4/473 (0.8%) 2/477 (0.4%)
Nasal inflammation 3/473 (0.6%) 3/477 (0.6%)
Nasal mucosal disorder 2/473 (0.4%) 2/477 (0.4%)
Nasal ulcer 2/473 (0.4%) 0/477 (0%)
Obstructive airways disorder 0/473 (0%) 1/477 (0.2%)
Oropharyngeal pain 11/473 (2.3%) 8/477 (1.7%)
Painful respiration 1/473 (0.2%) 0/477 (0%)
Pharyngeal inflammation 1/473 (0.2%) 0/477 (0%)
Pleural effusion 7/473 (1.5%) 8/477 (1.7%)
Pleuritic pain 1/473 (0.2%) 1/477 (0.2%)
Pneumomediastinum 1/473 (0.2%) 0/477 (0%)
Pneumonia aspiration 1/473 (0.2%) 0/477 (0%)
Pneumonitis 1/473 (0.2%) 4/477 (0.8%)
Pneumothorax 4/473 (0.8%) 0/477 (0%)
Productive cough 11/473 (2.3%) 9/477 (1.9%)
Pulmonary artery thrombosis 2/473 (0.4%) 0/477 (0%)
Pulmonary cavitation 0/473 (0%) 1/477 (0.2%)
Pulmonary embolism 3/473 (0.6%) 4/477 (0.8%)
Pulmonary haemorrhage 3/473 (0.6%) 0/477 (0%)
Pulmonary oedema 1/473 (0.2%) 0/477 (0%)
Rales 1/473 (0.2%) 0/477 (0%)
Respiratory distress 0/473 (0%) 1/477 (0.2%)
Respiratory failure 0/473 (0%) 1/477 (0.2%)
Respiratory tract congestion 0/473 (0%) 2/477 (0.4%)
Rhinitis allergic 1/473 (0.2%) 0/477 (0%)
Rhinitis atrophic 1/473 (0.2%) 0/477 (0%)
Rhinorrhoea 8/473 (1.7%) 6/477 (1.3%)
Rhonchi 1/473 (0.2%) 3/477 (0.6%)
Sinus congestion 1/473 (0.2%) 0/477 (0%)
Sinus disorder 2/473 (0.4%) 0/477 (0%)
Sneezing 1/473 (0.2%) 0/477 (0%)
Sputum discoloured 2/473 (0.4%) 0/477 (0%)
Stridor 1/473 (0.2%) 1/477 (0.2%)
Tachypnoea 0/473 (0%) 2/477 (0.4%)
Throat irritation 1/473 (0.2%) 3/477 (0.6%)
Upper respiratory tract congestion 1/473 (0.2%) 0/477 (0%)
Wheezing 2/473 (0.4%) 2/477 (0.4%)
Skin and subcutaneous tissue disorders
Acne 9/473 (1.9%) 9/477 (1.9%)
Alopecia 28/473 (5.9%) 18/477 (3.8%)
Blister 1/473 (0.2%) 0/477 (0%)
Decubitus ulcer 2/473 (0.4%) 3/477 (0.6%)
Dermatitis 3/473 (0.6%) 2/477 (0.4%)
Dermatitis acneiform 65/473 (13.7%) 64/477 (13.4%)
Dermatitis exfoliative 0/473 (0%) 1/477 (0.2%)
Dry skin 52/473 (11%) 58/477 (12.2%)
Ecchymosis 1/473 (0.2%) 0/477 (0%)
Eczema 3/473 (0.6%) 0/477 (0%)
Erythema 5/473 (1.1%) 12/477 (2.5%)
Exfoliative rash 4/473 (0.8%) 6/477 (1.3%)
Hair colour changes 8/473 (1.7%) 2/477 (0.4%)
Hair disorder 1/473 (0.2%) 0/477 (0%)
Hair growth abnormal 1/473 (0.2%) 1/477 (0.2%)
Hair texture abnormal 2/473 (0.4%) 0/477 (0%)
Hyperhidrosis 1/473 (0.2%) 2/477 (0.4%)
Hyperkeratosis 0/473 (0%) 1/477 (0.2%)
Hypertrichosis 0/473 (0%) 1/477 (0.2%)
Hypoaesthesia facial 0/473 (0%) 1/477 (0.2%)
Ingrowing nail 1/473 (0.2%) 3/477 (0.6%)
Intertrigo 1/473 (0.2%) 1/477 (0.2%)
Leukocytoclastic vasculitis 1/473 (0.2%) 0/477 (0%)
Madarosis 2/473 (0.4%) 1/477 (0.2%)
Nail bed inflammation 0/473 (0%) 1/477 (0.2%)
Nail discolouration 1/473 (0.2%) 0/477 (0%)
Nail discomfort 0/473 (0%) 1/477 (0.2%)
Nail disorder 4/473 (0.8%) 8/477 (1.7%)
Night sweats 2/473 (0.4%) 2/477 (0.4%)
Onychoclasis 2/473 (0.4%) 2/477 (0.4%)
Pain of skin 0/473 (0%) 2/477 (0.4%)
Palmar erythema 2/473 (0.4%) 0/477 (0%)
Palmar-plantar erythrodysaesthesia syndrome 42/473 (8.9%) 20/477 (4.2%)
Periorbital oedema 2/473 (0.4%) 1/477 (0.2%)
Petechiae 5/473 (1.1%) 2/477 (0.4%)
Photosensitivity reaction 2/473 (0.4%) 1/477 (0.2%)
Prurigo 0/473 (0%) 2/477 (0.4%)
Pruritus 33/473 (7%) 53/477 (11.1%)
Pruritus generalised 2/473 (0.4%) 1/477 (0.2%)
Psoriasis 0/473 (0%) 1/477 (0.2%)
Purpura 0/473 (0%) 1/477 (0.2%)
Rash 277/473 (58.6%) 255/477 (53.5%)
Rash erythematous 2/473 (0.4%) 2/477 (0.4%)
Rash follicular 1/473 (0.2%) 0/477 (0%)
Rash generalised 5/473 (1.1%) 3/477 (0.6%)
Rash macular 3/473 (0.6%) 5/477 (1%)
Rash maculo-papular 14/473 (3%) 13/477 (2.7%)
Rash papular 6/473 (1.3%) 6/477 (1.3%)
Rash pruritic 1/473 (0.2%) 3/477 (0.6%)
Rash scarlatiniform 1/473 (0.2%) 0/477 (0%)
Rash vesicular 0/473 (0%) 1/477 (0.2%)
Scab 1/473 (0.2%) 0/477 (0%)
Scar pain 0/473 (0%) 1/477 (0.2%)
Skin atrophy 0/473 (0%) 1/477 (0.2%)
Skin burning sensation 1/473 (0.2%) 1/477 (0.2%)
Skin chapped 1/473 (0.2%) 1/477 (0.2%)
Skin discolouration 3/473 (0.6%) 0/477 (0%)
Skin disorder 2/473 (0.4%) 0/477 (0%)
Skin exfoliation 5/473 (1.1%) 4/477 (0.8%)
Skin fissures 5/473 (1.1%) 14/477 (2.9%)
Skin haemorrhage 1/473 (0.2%) 0/477 (0%)
Skin hyperpigmentation 1/473 (0.2%) 2/477 (0.4%)
Skin hypopigmentation 1/473 (0.2%) 0/477 (0%)
Skin lesion 1/473 (0.2%) 1/477 (0.2%)
Skin maceration 1/473 (0.2%) 0/477 (0%)
Skin necrosis 0/473 (0%) 1/477 (0.2%)
Skin nodule 1/473 (0.2%) 0/477 (0%)
Skin reaction 1/473 (0.2%) 0/477 (0%)
Skin toxicity 1/473 (0.2%) 1/477 (0.2%)
Skin ulcer 2/473 (0.4%) 1/477 (0.2%)
Subcutaneous emphysema 1/473 (0.2%) 0/477 (0%)
Swelling face 5/473 (1.1%) 0/477 (0%)
Trichorrhexis 0/473 (0%) 1/477 (0.2%)
Urticaria 2/473 (0.4%) 0/477 (0%)
Xanthoma 0/473 (0%) 1/477 (0.2%)
Xeroderma 0/473 (0%) 1/477 (0.2%)
Yellow skin 7/473 (1.5%) 0/477 (0%)
Surgical and medical procedures
Skin neoplasm excision 1/473 (0.2%) 0/477 (0%)
Tooth extraction 1/473 (0.2%) 0/477 (0%)
Urethral dilation procedure 0/473 (0%) 1/477 (0.2%)
Vascular disorders
Angiodysplasia 0/473 (0%) 1/477 (0.2%)
Circulatory collapse 0/473 (0%) 1/477 (0.2%)
Deep vein thrombosis 0/473 (0%) 2/477 (0.4%)
Flushing 2/473 (0.4%) 2/477 (0.4%)
Haematoma 3/473 (0.6%) 1/477 (0.2%)
Hot flush 5/473 (1.1%) 1/477 (0.2%)
Hyperaemia 0/473 (0%) 2/477 (0.4%)
Hypertension 37/473 (7.8%) 11/477 (2.3%)
Hypotension 5/473 (1.1%) 5/477 (1%)
Jugular vein thrombosis 1/473 (0.2%) 0/477 (0%)
Lymphoedema 0/473 (0%) 1/477 (0.2%)
Orthostatic hypotension 2/473 (0.4%) 0/477 (0%)
Pallor 1/473 (0.2%) 0/477 (0%)
Peripheral coldness 2/473 (0.4%) 1/477 (0.2%)
Phlebitis 1/473 (0.2%) 0/477 (0%)
Subclavian vein thrombosis 1/473 (0.2%) 0/477 (0%)
Superior vena caval occlusion 1/473 (0.2%) 3/477 (0.6%)
Thrombophlebitis 1/473 (0.2%) 0/477 (0%)
Thrombosis 0/473 (0%) 2/477 (0.4%)
Venous insufficiency 1/473 (0.2%) 0/477 (0%)
Venous thrombosis limb 0/473 (0%) 1/477 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00457392
Other Study ID Numbers:
  • A6181087
  • SUN1087
First Posted:
Apr 6, 2007
Last Update Posted:
Oct 29, 2013
Last Verified:
Sep 1, 2013