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NSCLC: Trial Of CP-751, 871 And Erlotinib In Refractory Lung Cancer

Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT00673049
Collaborator
(none)
583
Enrollment
175
Locations
2
Arms
47
Duration (Months)
3.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to test a clinical benefit of the addition of CP 751,871 to erlotinib therapy in patients with advanced NSCLC of non adenocarcinoma histology. The primary endpoint is Overall Survival (OS).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This study was terminated on March 8, 2010 due to an analysis by an independent Data Safety Monitoring Committee (DSMC) indicating that the addition of CP-751,871 [figitumumab] to erlotinib [Tarceva] would be unlikely to meet the primary endpoint of improving overall survival when compared to erlotinib alone.

This Oncology study continues as terminated, however for ethical reasons some patients, noted with resultant benefit, continue receiving treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
583 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized, Open Label, Phase 3 Trial Of Erlotinib Alone Or In Combination With CP-751,871 In Patients With Advanced Non Small Cell Lung Cancer Of Non Adenocarcinoma Histology
Study Start Date :
May 1, 2008
Actual Primary Completion Date :
Mar 1, 2011
Actual Study Completion Date :
Apr 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

The CP 751,871 treatment in combination with erlotinib will be given in three week cycles. CP 751,871 (20 mg/kg) + erlotinib (150 mg/day) CP 751,871 will be administered as an IV infusion on study Days 1 and 2 in Cycle 1, and every three weeks (from Day 1) (Cycle) thereafter.

Drug: CP 751,871 (Figitumumab)
CP 751,871 (20 mg/kg) will be administered as an IV infusion on study Days 1 and 2 in Cycle 1, and every three weeks (from Day 1) (Cycle) thereafter.

Drug: Erlotinib
Erlotinib (one tablet of 150 mg/day PO).
Active Comparator: Arm B

Erlotinib (one tablet of 150 mg/day PO). Erlotinib will be taken at least one hour before or two hours after the ingestion of food)

Drug: Erlotinib
Erlotinib (one tablet of 150 mg/day PO). Erlotinib will be taken at least one hour before or two hours after the ingestion of food.

Outcome Measures

Primary Outcome Measures

  1. Overall Survival [Baseline, assessed every cycle until disease progression and then every 4 weeks until death, up to 30.65 months]

    The time from date of randomization to date of death due to any cause. For participants who were alive, overall survival was censored at the last contact.

Secondary Outcome Measures

  1. Progression Free Survival (PFS) [Baseline, 6, 9, 12, 15, 18 weeks after randomization, thereafter assessed every 6 weeks until disease progression during treatment (or every 8 weeks until disease progression during off-treatment), up to 29.7 months]

    Time from randomization to date of first documentation of progression or death due to any cause, whichever came first. Participants last known to be alive and progression-free, who had a baseline and at least 1 on-study disease assessment, were censored at last disease assessment verifying lack of progression. Progression was determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, unequivocal progression of non-target disease, or the appearance of new lesions.

  2. Percentage of Participants With Objective Response [Baseline, 6, 9, 12, 15, 18 weeks after randomization, thereafter assessed every 6 weeks until disease progression during treatment (or every 8 weeks until disease progression during off-treatment), up to 29.7 months]

    Percentage of participants with objective response (OR) based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. CR are defined as complete disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

  3. Maximum Observed Plasma Concentration (Cmax) for Figitumumab [Cycle 1 (Day 1 [predose], Day 2 [1 hour after end of infusion] ), Cycles 2, 4, 6 (predose), Cycle 5 (predose, 1 hour after end of infusion) for figi plus erlo group; Cycles 1, 2,4 (predose) for erlo, then figi group]

  4. Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab [Cycle 1 (Day 1 [predose], Day 2 [1 hour after end of infusion] ), Cycles 2, 4, 6 (predose), Cycle 5 (predose, 1 hour after end of infusion) for figi plus erlo group; Cycles 1, 2,4 (predose) for erlo, then figi group]

  5. Percentage of Participants Reporting Positive for Total Anti-drug Antibodies (ADA) [Cycles 1, 2, 4 (predose), End of Treatment ([EOT] 21-28 days after last dose), about 150 days after last figi dose for figi plus erlo group; Cycles 1, 2, 4 (predose), EOT, about 150 days after last figi dose for erlo, then figi group]

    ADAs are immunogenicity indicators to figitumumab. Participants reporting positive for ADAs are indicated by an endpoint titer of no less than 6.64.

  6. Counts of Circulating Tumor Cell (CTC) Expressing Positive Insulin-Like Growth Factor 1 Receptor (IGF-1R) [Baseline, Cycle 2 Day 1 (predose) and EOT (21-28 days after last dose)]

  7. Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility at Cycles 2, 3, Then Every Other Cycle and EOT (21-28 Days After Last Dose) [Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every other cycle and EOT (21-28 days after last dose)]

    EQ-5D is a 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. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

  8. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) at Cycles 2, 3, and Then Every Odd Cycle Starting With Cycle 5 and EOT (21-28 Days After Last Dose) [Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every odd cycle starting with Cycle 5 and EOT (21-28 days after last dose)]

    EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.

  9. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Score at Cycles 2, 3, and Then Every Odd Cycle Starting With Cycle 5, and EOT (21-28 Days After Last Dose) [Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every odd cycle starting with Cycle 5 and EOT (21-28 days after last dose)]

    QLQ-LC13 consists of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprise 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Non small cell lung cancer with a primary histology of squamous cell, large cell or adenosquamous carcinoma. At least 1 measurable lesion, as defined by RECIST.
Exclusion Criteria:

  • Primary NSCLC adenocarcinoma and its subtypes or unknown/unspecified histology.

  • Prior Erlotinib therapy.

  • Prior anti IGF IR based investigational therapy.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Pfizer Investigational Site Fort Smith Arkansas United States 72903
2 Pfizer Investigational Site Hot Springs Arkansas United States 71913
3 Pfizer Investigational Site Lakeport California United States 95453
4 Pfizer Investigational Site Orange California United States 92868-3298
5 Pfizer Investigational Site Orange California United States 92868
6 Pfizer Investigational Site Petaluma California United States 94954
7 Pfizer Investigational Site Santa Rosa California United States 95403
8 Pfizer Investigational Site Thousand Oaks California United States 91360
9 Pfizer Investigational Site Westlake Valley California United States 91360
10 Pfizer Investigational Site Denver Colorado United States 80205
11 Pfizer Investigational Site Lafayette Colorado United States 80026
12 Pfizer Investigational Site Hollywood Florida United States 33021
13 Pfizer Investigational Site Lake City Florida United States 32024
14 Pfizer Investigational Site Lake City Florida United States 32055
15 Pfizer Investigational Site Pembroke Pines Florida United States 33028
16 Pfizer Investigational Site Alpharetta Georgia United States 30005
17 Pfizer Investigational Site Atlanta Georgia United States 30308
18 Pfizer Investigational Site Atlanta Georgia United States 30322
19 Pfizer Investigational Site Atlanta Georgia United States 30342
20 Pfizer Investigational Site Conyers Georgia United States 30094
21 Pfizer Investigational Site Cumming Georgia United States 30041
22 Pfizer Investigational Site Decatur Georgia United States 30033
23 Pfizer Investigational Site Duluth Georgia United States 30096
24 Pfizer Investigational Site Lake Spivey Georgia United States 30236
25 Pfizer Investigational Site Lawrenceville Georgia United States 30046
26 Pfizer Investigational Site Snellville Georgia United States 30078
27 Pfizer Investigational Site Bloomington Illinois United States 61701
28 Pfizer Investigational Site Peoria Illinois United States 61615
29 Pfizer Investigational Site Beech Grove Indiana United States 46107
30 Pfizer Investigational Site Indianapolis Indiana United States 46237
31 Pfizer Investigational Site Indianapolis Indiana United States 46260
32 Pfizer Investigational Site Cedar Rapids Iowa United States 52402
33 Pfizer Investigational Site Waterloo Iowa United States 50701
34 Pfizer Investigational Site Louisville Kentucky United States 40207
35 Pfizer Investigational Site Bethesda Maryland United States 20817
36 Pfizer Investigational Site New Albany Mississippi United States 38652
37 Pfizer Investigational Site Billings Montana United States 59102
38 Pfizer Investigational Site Butte Montana United States 59701
39 Pfizer Investigational Site Lebanon New Hampshire United States 03756
40 Pfizer Investigational Site Manchester New Hampshire United States 03102
41 Pfizer Investigational Site Amherst New York United States 14221
42 Pfizer Investigational Site Bronx New York United States 10461
43 Pfizer Investigational Site Bronx New York United States 10467
44 Pfizer Investigational Site Buffalo New York United States 14263
45 Pfizer Investigational Site Lake Success New York United States 11042
46 Pfizer Investigational Site Manhasset New York United States 11030
47 Pfizer Investigational Site New Hyde Park New York United States 11040
48 Pfizer Investigational Site Columbus Ohio United States 43210
49 Pfizer Investigational Site Columbus Ohio United States 43221
50 Pfizer Investigational Site Norman Oklahoma United States 73071
51 Pfizer Investigational Site Oklahoma City Oklahoma United States 73102
52 Pfizer Investigational Site Oklahoma City Oklahoma United States 73109
53 Pfizer Investigational Site Oklahoma City Oklahoma United States 73120
54 Pfizer Investigational Site Tulsa Oklahoma United States 74104
55 Pfizer Investigational Site Tulsa Oklahoma United States 74133
56 Pfizer Investigational Site Tulsa Oklahoma United States 74136
57 Pfizer Investigational Site Philadelphia Pennsylvania United States 19104
58 Pfizer Investigational Site Philadelphia Pennsylvania United States 19107
59 Pfizer Investigational Site Germantown Tennessee United States 38138
60 Pfizer Investigational Site San Antonio Texas United States 78229
61 Pfizer Investigational Site Charlottesville Virginia United States 22908-0334
62 Pfizer Investigational Site Charlottesville Virginia United States 22908-0716
63 Pfizer Investigational Site Gloucester Virginia United States 23601
64 Pfizer Investigational Site Glouster Virginia United States 23061
65 Pfizer Investigational Site Newport News Virginia United States 23601
66 Pfizer Investigational Site Williamsburg Virginia United States 23185
67 Pfizer Investigational Site Wenatchee Washington United States 98801
68 Pfizer Investigational Site Wheeling West Virginia United States 26003-6300
69 Pfizer Investigational Site Cody Wyoming United States 82414
70 Pfizer Investigational Site Brasschaat Belgium 2930
71 Pfizer Investigational Site Mons Belgium 7000
72 Pfizer Investigational Site Rio de Janeiro RJ Brazil 20230 -130
73 Pfizer Investigational Site Rio de Janeiro RJ Brazil 20231 -050
74 Pfizer Investigational Site Porto Alegre RS Brazil 90035-903
75 Pfizer Investigational Site Higienopolis Sao Paulo/ Brazil Brazil 01224-010
76 Pfizer Investigational Site Santo André SP Brazil 09060-650
77 Pfizer Investigational Site Sao Paulo SP Brazil 01221-020
78 Pfizer Investigational Site Sao Paulo SP Brazil 01224-010
79 Pfizer Investigational Site São Paulo SP Brazil 01219-000
80 Pfizer Investigational Site Sofia Bulgaria 1233
81 Pfizer Investigational Site Sofia Bulgaria 1527
82 Pfizer Investigational Site Sofia Bulgaria 1756
83 Pfizer Investigational Site Varna Bulgaria 9000
84 Pfizer Investigational Site Toronto Ontario Canada M5G 2M9
85 Pfizer Investigational Site Montreal Quebec Canada H3T 1E2
86 Pfizer Investigational Site Independencia Santiago, RM Chile 8380455
87 Pfizer Investigational Site Kutna Hora Czech Republic 284 01
88 Pfizer Investigational Site Nova Ves pod Plesi Czech Republic 26204
89 Pfizer Investigational Site Praha 8 Czech Republic 180 81
90 Pfizer Investigational Site Tabor Czech Republic 390 03
91 Pfizer Investigational Site Rennes Cedex 9 France 35033
92 Pfizer Investigational Site BREST Cedex France 29609
93 Pfizer Investigational Site La Tronche France 38700
94 Pfizer Investigational Site Lille France 59020 Cedex
95 Pfizer Investigational Site Marseille Cedex 09 France 13009
96 Pfizer Investigational Site Marseille Cedex 20 France 13915
97 Pfizer Investigational Site Saint Pierre la Réunion Cedex France 97448
98 Pfizer Investigational Site St Priest En Jarez Cedex France 42277
99 Pfizer Investigational Site Villejuif France 94805
100 Pfizer Investigational Site Heraklion Crete Greece 71110
101 Pfizer Investigational Site Larisa Greece 41110
102 Pfizer Investigational Site Budapest Hungary 1525
103 Pfizer Investigational Site Matrahaza Hungary H-3233
104 Pfizer Investigational Site Szekesfehervar Hungary 8000
105 Pfizer Investigational Site Jakarta DKI Jakarta Indonesia 13230
106 Pfizer Investigational Site Surabaya East Java Indonesia 60286
107 Pfizer Investigational Site Cork Ireland
108 Pfizer Investigational Site Dublin 24 Ireland
109 Pfizer Investigational Site Dublin Ireland 8
110 Pfizer Investigational Site Avellino Italy 83100
111 Pfizer Investigational Site Aviano (PN) Italy 33081
112 Pfizer Investigational Site Cattolica (RN) Italy 47841
113 Pfizer Investigational Site Modena Italy 41100
114 Pfizer Investigational Site Orbassano (TO) Italy 10043
115 Pfizer Investigational Site Padova Italy 35128
116 Pfizer Investigational Site Rimini Italy 47900
117 Pfizer Investigational Site Roma Italy 00157
118 Pfizer Investigational Site Gyeonggi-do Korea, Republic of 410-769
119 Pfizer Investigational Site Seoul Korea, Republic of 120-752
120 Pfizer Investigational Site Seoul Korea, Republic of 138-736
121 Pfizer Investigational Site Riga Latvia LV 1002
122 Pfizer Investigational Site Riga Latvia LV 1079
123 Pfizer Investigational Site Bydgoszcz Poland 85-796
124 Pfizer Investigational Site Gdansk Poland 80-952
125 Pfizer Investigational Site Krakow Poland 31-108
126 Pfizer Investigational Site Krakow Poland 31-215
127 Pfizer Investigational Site Lublin Poland 20-954
128 Pfizer Investigational Site Olsztyn Poland 10-357
129 Pfizer Investigational Site Olsztyn Poland 10-513
130 Pfizer Investigational Site Rybnik Poland 44-200
131 Pfizer Investigational Site Wodzislaw Sl. Poland 44-300
132 Pfizer Investigational Site Ponce Puerto Rico 00716
133 Pfizer Investigational Site Cluj-Napoca Cluj Romania 400015
134 Pfizer Investigational Site Cluj-Napoca Romania 400015
135 Pfizer Investigational Site Iasi Romania 700106
136 Pfizer Investigational Site Krasnodar Russian Federation 350040
137 Pfizer Investigational Site Moscow Russian Federation 115478
138 Pfizer Investigational Site Moscow Russian Federation 143423
139 Pfizer Investigational Site Sochi Russian Federation 354057
140 Pfizer Investigational Site St-Petersburg Russian Federation 194044
141 Pfizer Investigational Site St. Petersburg Russian Federation 198255
142 Pfizer Investigational Site Belgrade Serbia 11000
143 Pfizer Investigational Site Sremska Kamenica Serbia 21204
144 Pfizer Investigational Site Ljubljana Slovenia 1000
145 Pfizer Investigational Site Bloemfontein South Africa 9301
146 Pfizer Investigational Site Cape Town South Africa 7925
147 Pfizer Investigational Site Elche Alicante Spain 03203
148 Pfizer Investigational Site Oviedo Asturias Spain 33006
149 Pfizer Investigational Site L'hospitalet de Llobregat Barcelona Spain 08097
150 Pfizer Investigational Site Manresa Barcelona Spain 08243
151 Pfizer Investigational Site Sabadell Barcelona Spain 08208
152 Pfizer Investigational Site Barcelona Spain 08025
153 Pfizer Investigational Site Girona Spain 17007
154 Pfizer Investigational Site Madrid Spain 28007
155 Pfizer Investigational Site Madrid Spain 28033
156 Pfizer Investigational Site Madrid Spain 28041
157 Pfizer Investigational Site Sevilla Spain 41009
158 Pfizer Investigational Site Sevilla Spain 41013
159 Pfizer Investigational Site Basel Switzerland CH-4031
160 Pfizer Investigational Site Basel Switzerland CH-4058
161 Pfizer Investigational Site CH-4101 Bruderholz Switzerland
162 Pfizer Investigational Site Chur Switzerland 7000
163 Pfizer Investigational Site Liestal Switzerland CH-4410
164 Pfizer Investigational Site Taichung Taiwan 404
165 Pfizer Investigational Site Taipei Taiwan 112
166 Pfizer Investigational Site Taoyuan County Taiwan 333
167 Pfizer Investigational Site Dnipropetrovsk Ukraine 49102
168 Pfizer Investigational Site Donetsk Ukraine 83092
169 Pfizer Investigational Site Kharkiv Ukraine 61070
170 Pfizer Investigational Site Kyiv Ukraine 03115
171 Pfizer Investigational Site Sumy Ukraine 40005
172 Pfizer Investigational Site Sutton Surrey United Kingdom SM2 5PT
173 Pfizer Investigational Site London United Kingdom SW3 6JJ
174 Pfizer Investigational Site London United Kingdom W6 8RF
175 Pfizer Investigational Site Manchester United Kingdom M20 4BX

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:
NCT00673049
Other Study ID Numbers:
  • A4021018
First Posted:
May 7, 2008
Last Update Posted:
Jul 24, 2013
Last Verified:
Jul 1, 2013
Keywords provided by Pfizer
IGR-1R
Non small cell lung cancer
CP-751
871
Figitumumab
Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Carcinoma, Large Cell
Carcinoma, Adenosquamous
Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Figitumumab + Erlotinib (Randomized to and Treated With) Erlotinib (Randomized to and Treated With) Randomized to Figi + Erlo Arm But Treated Only With Erlo Erlotinib, Then Figitumumab
Arm/Group Description Figitumumab ( [CP-751,871], figi) was given in combination with erlotinib (erlo) in 3-week cycles. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 milligram (mg) daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Figitumumab 20 mg/kg was given as a single-agent therapy to participants who had disease progression on erlotinib alone. Figitumumab was administered in 3-week cycles as IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter.
Period Title: Before Progression on Erlotinib
STARTED 292 290 1 0
Treated 289 289 1 0
COMPLETED 0 0 0 0
NOT COMPLETED 292 290 1 0
Period Title: Before Progression on Erlotinib
STARTED 0 0 0 83
COMPLETED 0 0 0 0
NOT COMPLETED 0 0 0 83

Baseline Characteristics

Arm/Group Title Figitumumab + Erlotinib (as Randomized) Erlotinib (as Randomized) Total
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycles. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg at least 1 hour before or 2 hours after the ingestion of food. Intent-to-treat population according to randomization was analyzed. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Intent-to-treat population according to randomization was analyzed. Total of all reporting groups
Overall Participants 293 290 583
Age, Customized (participants) [Number]
<70 years
226
77.1%
222
76.6%
448
76.8%
>=70 years
67
22.9%
68
23.4%
135
23.2%
Sex: Female, Male (Count of Participants)
Female
65
22.2%
65
22.4%
130
22.3%
Male
228
77.8%
225
77.6%
453
77.7%

Outcome Measures

1. Primary Outcome
Title Overall Survival
Description The time from date of randomization to date of death due to any cause. For participants who were alive, overall survival was censored at the last contact.
Time Frame Baseline, assessed every cycle until disease progression and then every 4 weeks until death, up to 30.65 months

Outcome Measure Data

Analysis Population Description
Full (intent-to-treat) analysis set, which included all participants randomized regardless of treatment received.
Arm/Group Title Figitumumab + Erlotinib Erlotinib
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycles. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Measure Participants 293 290
Median (95% Confidence Interval) [months]
5.7
6.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Figitumumab + Erlotinib, Erlotinib
Comments P-value was calculated using log-rank test stratified by gender (Male or Female), Eastern Cooperative Oncology Group (ECOG) performance status (less than or equal to [=<1] or 2), and region (United States/Canada, European Union, rest of world). The stratified Cox proportional hazards model was fitted to estimate the hazard ratio, using the same stratification variables as above.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.35
Comments One-sided significance level at alpha=0.024 was used. Two-sided p-value was reported.
Method Log Rank
Comments Nominal p-values were reported without adjustment for the interim analysis.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.091
Confidence Interval (2-Sided) 95%
0.909 to 1.310
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Progression Free Survival (PFS)
Description Time from randomization to date of first documentation of progression or death due to any cause, whichever came first. Participants last known to be alive and progression-free, who had a baseline and at least 1 on-study disease assessment, were censored at last disease assessment verifying lack of progression. Progression was determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, unequivocal progression of non-target disease, or the appearance of new lesions.
Time Frame Baseline, 6, 9, 12, 15, 18 weeks after randomization, thereafter assessed every 6 weeks until disease progression during treatment (or every 8 weeks until disease progression during off-treatment), up to 29.7 months

Outcome Measure Data

Analysis Population Description
Full (intent-to-treat) analysis set, which included all participants randomized regardless of treatment received.
Arm/Group Title Figitumumab + Erlotinib Erlotinib
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycles. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Measure Participants 293 290
Median (95% Confidence Interval) [months]
2.1
2.6
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Figitumumab + Erlotinib, Erlotinib
Comments P-value was calculated using log-rank test stratified by gender (Male or Female), ECOG performance status (less than or equal to [=<1] or 2), and region (United States/Canada, European Union, rest of world). The stratified Cox proportional hazards model was fitted to estimate the hazard ratio, using the same stratification variables as above.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.426
Comments One-sided significance level at alpha=0.001 was used. Two-sided p-value was reported.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.075
Confidence Interval (2-Sided) 95%
0.898 to 1.287
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Percentage of Participants With Objective Response
Description Percentage of participants with objective response (OR) based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. CR are defined as complete disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame Baseline, 6, 9, 12, 15, 18 weeks after randomization, thereafter assessed every 6 weeks until disease progression during treatment (or every 8 weeks until disease progression during off-treatment), up to 29.7 months

Outcome Measure Data

Analysis Population Description
Full (intent-to-treat) analysis set, which included all participants randomized regardless of treatment received.
Arm/Group Title Figitumumab + Erlotinib Erlotinib
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycles. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Measure Participants 293 290
Number (95% Confidence Interval) [percentage of participants]
5.5
1.9%
3.8
1.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Figitumumab + Erlotinib, Erlotinib
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.338
Comments
Method Chi-squared
Comments
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 1.668
Confidence Interval (2-Sided) 95%
-1.7 to 5.1
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Figitumumab
Description
Time Frame Cycle 1 (Day 1 [predose], Day 2 [1 hour after end of infusion] ), Cycles 2, 4, 6 (predose), Cycle 5 (predose, 1 hour after end of infusion) for figi plus erlo group; Cycles 1, 2,4 (predose) for erlo, then figi group

Outcome Measure Data

Analysis Population Description
Due to futility, the study was terminated early; therefore pharmacokinetic data were not analyzed.
Arm/Group Title Figitumumab + Erlotinib, and Erlotinib Then Figitumumab
Arm/Group Description Participants who received figitumumab (20 mg/kg), whether figitumumab was given in combination with erlotinib (150 mg/day) from the beginning or figitumumab was given after disease progression with erlotinib (150 mg/day) alone. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter.
Measure Participants 0
5. Secondary Outcome
Title Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab
Description
Time Frame Cycle 1 (Day 1 [predose], Day 2 [1 hour after end of infusion] ), Cycles 2, 4, 6 (predose), Cycle 5 (predose, 1 hour after end of infusion) for figi plus erlo group; Cycles 1, 2,4 (predose) for erlo, then figi group

Outcome Measure Data

Analysis Population Description
Due to futility, the study was terminated early; therefore pharmacokinetic data were not analyzed.
Arm/Group Title Figitumumab + Erlotinib, and Erlotinib Then Figitumumab
Arm/Group Description Participants who received figitumumab (20 mg/kg), whether figitumumab was given in combination with erlotinib (150 mg/day) from the beginning or figitumumab was given after disease progression with erlotinib (150 mg/day) alone. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter.
Measure Participants 0
6. Secondary Outcome
Title Percentage of Participants Reporting Positive for Total Anti-drug Antibodies (ADA)
Description ADAs are immunogenicity indicators to figitumumab. Participants reporting positive for ADAs are indicated by an endpoint titer of no less than 6.64.
Time Frame Cycles 1, 2, 4 (predose), End of Treatment ([EOT] 21-28 days after last dose), about 150 days after last figi dose for figi plus erlo group; Cycles 1, 2, 4 (predose), EOT, about 150 days after last figi dose for erlo, then figi group

Outcome Measure Data

Analysis Population Description
Analysis population included all participants treated with figi. Data are combined for "figi+erlo" and "erlo then figi" because the objective was to report any participants with positive ADA after exposure to figi regardless of figi administration order, rather comparison of these 2 treatment groups. N=number of participants evaluable.
Arm/Group Title Figitumumab + Erlotinib, and Erlotinib Then Figitumumab
Arm/Group Description Participants who received figitumumab (20 mg/kg), whether figitumumab was given in combination with erlotinib (150 mg/day) from the beginning or figitumumab was given after disease progression with erlotinib (150 mg/day) alone. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter.
Measure Participants 360
Number [percentage of participants]
0.28
0.1%
7. Secondary Outcome
Title Counts of Circulating Tumor Cell (CTC) Expressing Positive Insulin-Like Growth Factor 1 Receptor (IGF-1R)
Description
Time Frame Baseline, Cycle 2 Day 1 (predose) and EOT (21-28 days after last dose)

Outcome Measure Data

Analysis Population Description
Due to futility, the study was terminated early; therefore biomarker results were not analyzed.
Arm/Group Title Figitumumab + Erlotinib, and Erlotinib Then Figitumumab
Arm/Group Description Participants who received figitumumab (20 mg/kg), whether figitumumab was given in combination with erlotinib (150 mg/day) from the beginning or figitumumab was given after disease progression with erlotinib (150 mg/day) alone. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter.
Measure Participants 0
8. Secondary Outcome
Title Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility at Cycles 2, 3, Then Every Other Cycle and EOT (21-28 Days After Last Dose)
Description EQ-5D is a 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. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time Frame Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every other cycle and EOT (21-28 days after last dose)

Outcome Measure Data

Analysis Population Description
Due to futility, the study was terminated early; therefore EQ-5D data were not analyzed.
Arm/Group Title Figitumumab + Erlotinib Erlotinib
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycles. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Measure Participants 0 0
9. Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) at Cycles 2, 3, and Then Every Odd Cycle Starting With Cycle 5 and EOT (21-28 Days After Last Dose)
Description EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Time Frame Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every odd cycle starting with Cycle 5 and EOT (21-28 days after last dose)

Outcome Measure Data

Analysis Population Description
This outcome measure was added in Protocol Amendment 3 (28 January 2010). However, data were not collected as the majority of the subjects had already been enrolled prior to this amendment and the study was terminated shortly thereafter (02 March 2010).
Arm/Group Title Figitumumab + Erlotinib Erlotinib
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycles. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Measure Participants 0 0
10. Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Score at Cycles 2, 3, and Then Every Odd Cycle Starting With Cycle 5, and EOT (21-28 Days After Last Dose)
Description QLQ-LC13 consists of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprise 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
Time Frame Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every odd cycle starting with Cycle 5 and EOT (21-28 days after last dose)

Outcome Measure Data

Analysis Population Description
This outcome measure was added in Protocol Amendment 3 (28 January 2010). However, data were not collected as the majority of the subjects had already been enrolled prior to this amendment and the study was terminated shortly thereafter (02 March 2010).
Arm/Group Title Figitumumab + Erlotinib Erlotinib
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycles. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Measure Participants 0 0

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. All treated subjects were analyzed for AEs and SAEs.
Arm/Group Title Figitumumab + Erlotinib Erlotinib Erlotinib, Then Figitumumab
Arm/Group Description Figitumumab (20 mg/kg) in combination with erlotinib (150 mg/day) was given in 3-week cycle. Figitumumab was administered as an IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every three weeks (from Day 1) thereafter. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food. Figitumumab (20 mg/kg) was given as a single agent after participants had disease progression on erlotinib alone. Figitumumab was given in 3-week cycles as IV infusion on study Days 1 and 2 in Cycle 1, and on Day 1 every 3 weeks (from Day 1) thereafter.
All Cause Mortality
Figitumumab + Erlotinib Erlotinib Erlotinib, Then Figitumumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Figitumumab + Erlotinib Erlotinib Erlotinib, Then Figitumumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 204/289 (70.6%) 153/290 (52.8%) 63/83 (75.9%)
Blood and lymphatic system disorders
Anaemia 3/289 (1%) 3/290 (1%) 2/83 (2.4%)
Thrombocytopenia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Febrile neutropenia 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Neutropenia 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Cardiac disorders
Cardiac failure 2/289 (0.7%) 0/290 (0%) 1/83 (1.2%)
Arrhythmia 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Cardiac arrest 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Acute myocardial infarction 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Bradycardia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Atrial tachycardia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Cardiac failure congestive 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pericardial effusion 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pericarditis constrictive 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Supraventricular tachycardia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Ear and labyrinth disorders
Deafness bilateral 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Gastrointestinal disorders
Diarrhoea 11/289 (3.8%) 3/290 (1%) 0/83 (0%)
Vomiting 4/289 (1.4%) 3/290 (1%) 1/83 (1.2%)
Abdominal pain 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Dysphagia 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Gastrointestinal haemorrhage 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Gastric ulcer 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Intestinal ischaemia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Mouth ulceration 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Nausea 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Oesophagitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Rectal haemorrhage 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Stomatitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Upper gastrointestinal haemorrhage 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Colitis 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Ileus 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Inguinal hernia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Intestinal obstruction 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Large intestine perforation 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Oesophageal stenosis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pancreatitis 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Peritonitis 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Small intestinal obstruction 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
General disorders
Disease progression 136/289 (47.1%) 112/290 (38.6%) 45/83 (54.2%)
Asthenia 5/289 (1.7%) 1/290 (0.3%) 0/83 (0%)
Chest pain 5/289 (1.7%) 0/290 (0%) 1/83 (1.2%)
Pyrexia 4/289 (1.4%) 5/290 (1.7%) 1/83 (1.2%)
General physical health deterioration 3/289 (1%) 5/290 (1.7%) 5/83 (6%)
Pain 3/289 (1%) 0/290 (0%) 0/83 (0%)
Death 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Fatigue 2/289 (0.7%) 1/290 (0.3%) 1/83 (1.2%)
Chills 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hypothermia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Oedema peripheral 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Mucosal inflammation 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Hepatobiliary disorders
Hepatic function abnormal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Cholecystitis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Hyperbilirubinaemia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Immune system disorders
Hypersensitivity 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Anaphylactic reaction 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Infections and infestations
Pneumonia 9/289 (3.1%) 12/290 (4.1%) 1/83 (1.2%)
Lower respiratory tract infection 4/289 (1.4%) 0/290 (0%) 1/83 (1.2%)
Respiratory tract infection 4/289 (1.4%) 3/290 (1%) 0/83 (0%)
Gastroenteritis 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Sepsis 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Bacteraemia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Bronchopneumonia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Clostridium difficile colitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Fungaemia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Gangrene 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Infection 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Lung abscess 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Lung infection 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Osteomyelitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Perirectal abscess 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Pneumonia bacterial 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Pulmonary tuberculosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Pyelonephritis acute 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Septic shock 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Urinary tract infection 1/289 (0.3%) 2/290 (0.7%) 0/83 (0%)
Empyema 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Paronychia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pseudomonas infection 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pyothorax 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Staphylococcal infection 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Urosepsis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Injury, poisoning and procedural complications
Collapse of lung 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Fall 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Concussion 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Femoral neck fracture 0/289 (0%) 0/290 (0%) 2/83 (2.4%)
Road traffic accident 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Investigations
Band neutrophil count increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Blood creatinine increased 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Gamma-glutamyltransferase increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
General physical condition abnormal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Haematocrit decreased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Liver function test abnormal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Myocardial strain 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Renal function test abnormal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Troponin increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
White blood cell count increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Metabolism and nutrition disorders
Dehydration 14/289 (4.8%) 6/290 (2.1%) 1/83 (1.2%)
Hyperglycaemia 7/289 (2.4%) 0/290 (0%) 2/83 (2.4%)
Hypercalcaemia 6/289 (2.1%) 4/290 (1.4%) 1/83 (1.2%)
Decreased appetite 4/289 (1.4%) 1/290 (0.3%) 0/83 (0%)
Diabetes mellitus 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Diabetes mellitus inadequate control 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Diabetic ketoacidosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Failure to thrive 1/289 (0.3%) 2/290 (0.7%) 0/83 (0%)
Hyponatraemia 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Hypophosphataemia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hypoglycaemia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Malnutrition 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Musculoskeletal and connective tissue disorders
Neck pain 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Back pain 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Muscular weakness 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression 6/289 (2.1%) 2/290 (0.7%) 2/83 (2.4%)
Lung neoplasm malignant 2/289 (0.7%) 4/290 (1.4%) 1/83 (1.2%)
Non-small cell lung cancer 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Sebaceous carcinoma 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Rectal cancer 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Nervous system disorders
Syncope 5/289 (1.7%) 1/290 (0.3%) 0/83 (0%)
Cerebrovascular accident 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Convulsion 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Intraventricular haemorrhage 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Lethargy 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Balance disorder 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Cerebral haemorrhage 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Dysarthria 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Mental impairment 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Spinal cord compression 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Psychiatric disorders
Mental status changes 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Completed suicide 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Confusional state 0/289 (0%) 2/290 (0.7%) 1/83 (1.2%)
Renal and urinary disorders
Renal failure 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Renal failure acute 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Haematuria 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Urinary retention 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 11/289 (3.8%) 2/290 (0.7%) 1/83 (1.2%)
Pneumothorax 5/289 (1.7%) 1/290 (0.3%) 2/83 (2.4%)
Respiratory failure 5/289 (1.7%) 5/290 (1.7%) 0/83 (0%)
Haemoptysis 4/289 (1.4%) 6/290 (2.1%) 2/83 (2.4%)
Pulmonary haemorrhage 3/289 (1%) 3/290 (1%) 1/83 (1.2%)
Pleural effusion 2/289 (0.7%) 3/290 (1%) 1/83 (1.2%)
Pneumonia aspiration 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Respiratory distress 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Acute pulmonary oedema 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Acute respiratory distress syndrome 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Acute respiratory failure 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Alveolitis allergic 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Asphyxia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Aspiration 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Pneumonitis 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Pulmonary oedema 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Chronic obstructive pulmonary disease 0/289 (0%) 4/290 (1.4%) 0/83 (0%)
Dyspnoea at rest 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Hydropneumothorax 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Hypoxia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Oesophagobronchial fistula 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pulmonary embolism 0/289 (0%) 0/290 (0%) 2/83 (2.4%)
Skin and subcutaneous tissue disorders
Rash 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Skin reaction 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Drug eruption 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Vascular disorders
Deep vein thrombosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Haemorrhage 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hypertension 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hypotension 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Superior vena cava syndrome 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Arterial thrombosis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Other (Not Including Serious) Adverse Events
Figitumumab + Erlotinib Erlotinib Erlotinib, Then Figitumumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 265/289 (91.7%) 265/290 (91.4%) 79/83 (95.2%)
Blood and lymphatic system disorders
Anaemia 28/289 (9.7%) 26/290 (9%) 11/83 (13.3%)
Eosinophilia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Haematotoxicity 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Iron deficiency anaemia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Leukocytosis 2/289 (0.7%) 1/290 (0.3%) 2/83 (2.4%)
Leukopenia 4/289 (1.4%) 2/290 (0.7%) 0/83 (0%)
Lymph node pain 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Lymphadenopathy 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Lymphopenia 3/289 (1%) 1/290 (0.3%) 0/83 (0%)
Neutropenia 5/289 (1.7%) 2/290 (0.7%) 2/83 (2.4%)
Thrombocytopenia 8/289 (2.8%) 3/290 (1%) 1/83 (1.2%)
Cardiac disorders
Arrhythmia 0/289 (0%) 0/290 (0%) 2/83 (2.4%)
Atrial fibrillation 0/289 (0%) 3/290 (1%) 0/83 (0%)
Atrial flutter 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Atrioventricular block 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Cardiac failure 3/289 (1%) 0/290 (0%) 0/83 (0%)
Cardiac failure congestive 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Cardiomyopathy 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Coronary artery insufficiency 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Myocardial ischaemia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Palpitations 1/289 (0.3%) 4/290 (1.4%) 0/83 (0%)
Sinus arrhythmia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Sinus tachycardia 2/289 (0.7%) 0/290 (0%) 1/83 (1.2%)
Supraventricular extrasystoles 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Supraventricular tachycardia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Tachycardia 3/289 (1%) 4/290 (1.4%) 1/83 (1.2%)
Ventricular extrasystoles 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Ear and labyrinth disorders
Deafness 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Deafness neurosensory 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Deafness unilateral 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Ear disorder 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Ear pain 1/289 (0.3%) 1/290 (0.3%) 1/83 (1.2%)
Hearing impaired 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Tinnitus 3/289 (1%) 2/290 (0.7%) 0/83 (0%)
Tympanic membrane perforation 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Vertigo 3/289 (1%) 0/290 (0%) 0/83 (0%)
Vertigo positional 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Vestibular disorder 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Endocrine disorders
Adrenal insufficiency 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Cushing's syndrome 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hyperthyroidism 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Eye disorders
Abnormal sensation in eye 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Blepharitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Blindness 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Cataract 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Conjunctival hyperaemia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Conjunctivitis 10/289 (3.5%) 14/290 (4.8%) 2/83 (2.4%)
Conjunctivitis allergic 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Dry eye 2/289 (0.7%) 5/290 (1.7%) 1/83 (1.2%)
Eye inflammation 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Eye irritation 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Eye pain 1/289 (0.3%) 2/290 (0.7%) 1/83 (1.2%)
Eye pruritus 4/289 (1.4%) 3/290 (1%) 1/83 (1.2%)
Eye swelling 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Eyelid oedema 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Keratitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Keratoconjunctivitis sicca 3/289 (1%) 0/290 (0%) 0/83 (0%)
Lacrimation increased 5/289 (1.7%) 0/290 (0%) 0/83 (0%)
Ocular hyperaemia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Ocular icterus 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Ocular toxicity 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Photophobia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Uveitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Vision blurred 3/289 (1%) 0/290 (0%) 0/83 (0%)
Visual acuity reduced 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Gastrointestinal disorders
Abdominal pain upper 8/289 (2.8%) 8/290 (2.8%) 5/83 (6%)
Constipation 17/289 (5.9%) 19/290 (6.6%) 9/83 (10.8%)
Diarrhoea 123/289 (42.6%) 106/290 (36.6%) 10/83 (12%)
Dysphagia 14/289 (4.8%) 11/290 (3.8%) 6/83 (7.2%)
Mouth ulceration 16/289 (5.5%) 4/290 (1.4%) 1/83 (1.2%)
Nausea 54/289 (18.7%) 36/290 (12.4%) 8/83 (9.6%)
Stomatitis 18/289 (6.2%) 6/290 (2.1%) 0/83 (0%)
Vomiting 49/289 (17%) 23/290 (7.9%) 7/83 (8.4%)
Abdominal discomfort 1/289 (0.3%) 3/290 (1%) 1/83 (1.2%)
Abdominal distension 3/289 (1%) 2/290 (0.7%) 1/83 (1.2%)
Abdominal pain 10/289 (3.5%) 9/290 (3.1%) 3/83 (3.6%)
Abdominal pain lower 0/289 (0%) 2/290 (0.7%) 1/83 (1.2%)
Aerophagia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Anal fissure 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Aphthous stomatitis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Chapped lips 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Cheilitis 1/289 (0.3%) 3/290 (1%) 0/83 (0%)
Diverticulum 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Dry mouth 6/289 (2.1%) 8/290 (2.8%) 1/83 (1.2%)
Duodenal ulcer 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Dyspepsia 5/289 (1.7%) 3/290 (1%) 1/83 (1.2%)
Enterocolitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Erosive duodenitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Faecal incontinence 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Faeces discoloured 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Flatulence 3/289 (1%) 1/290 (0.3%) 0/83 (0%)
Gastric dilatation 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Gastric disorder 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Gastric ulcer 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Gastritis 1/289 (0.3%) 1/290 (0.3%) 1/83 (1.2%)
Gastrooesophageal reflux disease 2/289 (0.7%) 5/290 (1.7%) 2/83 (2.4%)
Gingival bleeding 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Gingival disorder 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Gingival pain 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Gingivitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Glossitis 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Haematemesis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Haematochezia 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Haemorrhoidal haemorrhage 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Haemorrhoids 4/289 (1.4%) 2/290 (0.7%) 2/83 (2.4%)
Ileus 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Intestinal obstruction 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Lip swelling 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Melaena 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Mouth haemorrhage 1/289 (0.3%) 2/290 (0.7%) 0/83 (0%)
Odynophagia 1/289 (0.3%) 2/290 (0.7%) 0/83 (0%)
Oesophageal pain 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Oesophageal stenosis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Oesophagitis 2/289 (0.7%) 1/290 (0.3%) 1/83 (1.2%)
Oral pain 4/289 (1.4%) 2/290 (0.7%) 1/83 (1.2%)
Paraesthesia oral 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Peptic ulcer 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Proctalgia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Rectal haemorrhage 5/289 (1.7%) 1/290 (0.3%) 0/83 (0%)
Retching 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Salivary gland disorder 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Subileus 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Tooth socket haemorrhage 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Toothache 2/289 (0.7%) 2/290 (0.7%) 1/83 (1.2%)
Upper gastrointestinal haemorrhage 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
General disorders
Asthenia 79/289 (27.3%) 46/290 (15.9%) 25/83 (30.1%)
Chest pain 31/289 (10.7%) 28/290 (9.7%) 21/83 (25.3%)
Fatigue 65/289 (22.5%) 53/290 (18.3%) 16/83 (19.3%)
Mucosal inflammation 33/289 (11.4%) 11/290 (3.8%) 0/83 (0%)
Oedema peripheral 8/289 (2.8%) 16/290 (5.5%) 1/83 (1.2%)
Pyrexia 25/289 (8.7%) 18/290 (6.2%) 5/83 (6%)
Axillary pain 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Chest discomfort 4/289 (1.4%) 2/290 (0.7%) 0/83 (0%)
Chills 4/289 (1.4%) 3/290 (1%) 1/83 (1.2%)
Disease progression 6/289 (2.1%) 4/290 (1.4%) 3/83 (3.6%)
Early satiety 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Face oedema 2/289 (0.7%) 2/290 (0.7%) 0/83 (0%)
Facial pain 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Feeling cold 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Gait disturbance 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
General physical health deterioration 4/289 (1.4%) 1/290 (0.3%) 0/83 (0%)
Hyperthermia 1/289 (0.3%) 3/290 (1%) 0/83 (0%)
Influenza like illness 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Infusion site pain 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Irritability 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Localised oedema 0/289 (0%) 3/290 (1%) 0/83 (0%)
Malaise 2/289 (0.7%) 1/290 (0.3%) 1/83 (1.2%)
Medical device pain 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Non-cardiac chest pain 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Oedema 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Pain 5/289 (1.7%) 7/290 (2.4%) 3/83 (3.6%)
Performance status decreased 2/289 (0.7%) 0/290 (0%) 1/83 (1.2%)
Ulcer 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Xerosis 1/289 (0.3%) 5/290 (1.7%) 1/83 (1.2%)
Hepatobiliary disorders
Cholelithiasis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Cholestasis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Cytolytic hepatitis 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Hepatic function abnormal 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Hepatotoxicity 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Hyperbilirubinaemia 3/289 (1%) 4/290 (1.4%) 1/83 (1.2%)
Jaundice 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Immune system disorders
Anaphylactic reaction 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Contrast media allergy 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Drug hypersensitivity 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hypersensitivity 5/289 (1.7%) 0/290 (0%) 0/83 (0%)
Infections and infestations
Paronychia 17/289 (5.9%) 8/290 (2.8%) 1/83 (1.2%)
Acne pustular 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Acute sinusitis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Bronchitis 5/289 (1.7%) 7/290 (2.4%) 3/83 (3.6%)
Candidiasis 3/289 (1%) 0/290 (0%) 0/83 (0%)
Cellulitis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Clostridial infection 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Device related infection 3/289 (1%) 0/290 (0%) 0/83 (0%)
Diverticulitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Ear infection 1/289 (0.3%) 1/290 (0.3%) 1/83 (1.2%)
Eye infection bacterial 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Folliculitis 2/289 (0.7%) 2/290 (0.7%) 0/83 (0%)
Fungal infection 1/289 (0.3%) 1/290 (0.3%) 1/83 (1.2%)
Gastroenteritis 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Herpes zoster 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Infection 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Influenza 3/289 (1%) 0/290 (0%) 0/83 (0%)
Laryngitis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Localised infection 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Lower respiratory tract infection 1/289 (0.3%) 3/290 (1%) 1/83 (1.2%)
Lung infection 5/289 (1.7%) 3/290 (1%) 2/83 (2.4%)
Mediastinitis 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Nail bed infection 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Nail infection 2/289 (0.7%) 2/290 (0.7%) 0/83 (0%)
Nasopharyngitis 2/289 (0.7%) 2/290 (0.7%) 1/83 (1.2%)
Oesophageal candidiasis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Omphalitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Onychomycosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Oral candidiasis 3/289 (1%) 4/290 (1.4%) 2/83 (2.4%)
Oral herpes 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Oropharyngeal candidiasis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Otitis externa 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Pharyngitis 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Pneumonia 6/289 (2.1%) 3/290 (1%) 0/83 (0%)
Post procedural infection 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pyothorax 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Rash pustular 4/289 (1.4%) 2/290 (0.7%) 1/83 (1.2%)
Respiratory moniliasis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Respiratory tract infection 2/289 (0.7%) 3/290 (1%) 2/83 (2.4%)
Rhinitis 3/289 (1%) 3/290 (1%) 0/83 (0%)
Sepsis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Sinusitis 2/289 (0.7%) 2/290 (0.7%) 2/83 (2.4%)
Skin candida 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Skin infection 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Sputum purulent 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Staphylococcal infection 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Tinea pedis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Tooth infection 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Tracheobronchitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Upper respiratory tract infection 4/289 (1.4%) 0/290 (0%) 1/83 (1.2%)
Urethritis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Urinary tract infection 8/289 (2.8%) 6/290 (2.1%) 0/83 (0%)
Urinary tract infection enterococcal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Vaginal infection 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Injury, poisoning and procedural complications
Back injury 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Bite 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Contusion 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Eschar 1/289 (0.3%) 1/290 (0.3%) 1/83 (1.2%)
Excoriation 1/289 (0.3%) 3/290 (1%) 0/83 (0%)
Fall 4/289 (1.4%) 0/290 (0%) 1/83 (1.2%)
Foot fracture 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Humerus fracture 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Joint injury 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Laceration 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Pelvic fracture 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Radiation pneumonitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Spinal compression fracture 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Toxicity to various agents 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Tracheal obstruction 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Wound 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Wound complication 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Investigations
Weight decreased 65/289 (22.5%) 33/290 (11.4%) 19/83 (22.9%)
Activated partial thromboplastin time prolonged 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Alanine aminotransferase increased 7/289 (2.4%) 10/290 (3.4%) 1/83 (1.2%)
Aspartate aminotransferase increased 5/289 (1.7%) 10/290 (3.4%) 1/83 (1.2%)
Blood alkaline phosphatase increased 6/289 (2.1%) 7/290 (2.4%) 0/83 (0%)
Blood bilirubin increased 2/289 (0.7%) 3/290 (1%) 0/83 (0%)
Blood calcium increased 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Blood cholesterol increased 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Blood creatine increased 4/289 (1.4%) 0/290 (0%) 0/83 (0%)
Blood creatinine increased 12/289 (4.2%) 3/290 (1%) 3/83 (3.6%)
Blood glucose increased 3/289 (1%) 1/290 (0.3%) 1/83 (1.2%)
Blood lactate dehydrogenase increased 1/289 (0.3%) 4/290 (1.4%) 0/83 (0%)
Blood magnesium decreased 3/289 (1%) 1/290 (0.3%) 0/83 (0%)
Blood potassium increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Blood urea increased 3/289 (1%) 3/290 (1%) 1/83 (1.2%)
Blood urea nitrogen/creatinine ratio increased 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Blood uric acid increased 4/289 (1.4%) 0/290 (0%) 2/83 (2.4%)
Body temperature increased 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Brain natriuretic peptide increased 4/289 (1.4%) 2/290 (0.7%) 4/83 (4.8%)
Breath sounds abnormal 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Clostridium test positive 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Electrocardiogram abnormal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Gamma-glutamyltransferase increased 13/289 (4.5%) 6/290 (2.1%) 3/83 (3.6%)
General physical condition abnormal 3/289 (1%) 0/290 (0%) 0/83 (0%)
Glycosylated haemoglobin increased 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Haemoglobin decreased 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Hepatic enzyme increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
International normalised ratio increased 1/289 (0.3%) 1/290 (0.3%) 2/83 (2.4%)
Liver function test abnormal 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Nutritional condition abnormal 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Platelet count increased 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Protein urine 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Prothrombin time prolonged 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Prothrombin time shortened 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Renal function test abnormal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Respiratory rate decreased 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Transaminases increased 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Troponin I increased 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Weight increased 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
White blood cell count increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
White blood cells urine positive 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Metabolism and nutrition disorders
Decreased appetite 115/289 (39.8%) 70/290 (24.1%) 32/83 (38.6%)
Dehydration 21/289 (7.3%) 6/290 (2.1%) 2/83 (2.4%)
Hyperglycaemia 37/289 (12.8%) 13/290 (4.5%) 12/83 (14.5%)
Cachexia 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Diabetes mellitus 6/289 (2.1%) 0/290 (0%) 3/83 (3.6%)
Diabetes mellitus inadequate control 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Electrolyte imbalance 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Failure to thrive 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Fluid overload 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Gout 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Hypercalcaemia 5/289 (1.7%) 6/290 (2.1%) 3/83 (3.6%)
Hyperkalaemia 4/289 (1.4%) 2/290 (0.7%) 0/83 (0%)
Hypermagnesaemia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Hypernatraemia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Hyperuricaemia 6/289 (2.1%) 0/290 (0%) 0/83 (0%)
Hypoalbuminaemia 1/289 (0.3%) 3/290 (1%) 0/83 (0%)
Hypoglycaemia 3/289 (1%) 3/290 (1%) 0/83 (0%)
Hypokalaemia 3/289 (1%) 5/290 (1.7%) 1/83 (1.2%)
Hypomagnesaemia 4/289 (1.4%) 3/290 (1%) 1/83 (1.2%)
Hyponatraemia 5/289 (1.7%) 4/290 (1.4%) 1/83 (1.2%)
Hypophagia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hypophosphataemia 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Metabolic acidosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Polydipsia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Vitamin D deficiency 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 11/289 (3.8%) 11/290 (3.8%) 5/83 (6%)
Back pain 19/289 (6.6%) 25/290 (8.6%) 9/83 (10.8%)
Musculoskeletal chest pain 7/289 (2.4%) 5/290 (1.7%) 6/83 (7.2%)
Musculoskeletal pain 7/289 (2.4%) 9/290 (3.1%) 7/83 (8.4%)
Pain in extremity 15/289 (5.2%) 5/290 (1.7%) 1/83 (1.2%)
Bone pain 6/289 (2.1%) 6/290 (2.1%) 1/83 (1.2%)
Chondrocalcinosis pyrophosphate 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Flank pain 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Groin pain 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Hypercreatinaemia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Joint range of motion decreased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Joint stiffness 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Limb discomfort 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Muscle atrophy 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Muscle spasms 14/289 (4.8%) 7/290 (2.4%) 4/83 (4.8%)
Muscular weakness 5/289 (1.7%) 2/290 (0.7%) 1/83 (1.2%)
Musculoskeletal discomfort 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Musculoskeletal disorder 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Musculoskeletal stiffness 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Myalgia 4/289 (1.4%) 4/290 (1.4%) 2/83 (2.4%)
Neck pain 2/289 (0.7%) 4/290 (1.4%) 1/83 (1.2%)
Osteoporosis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pain in jaw 0/289 (0%) 3/290 (1%) 1/83 (1.2%)
Pathological fracture 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Plantar fasciitis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Sensation of heaviness 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain 2/289 (0.7%) 0/290 (0%) 1/83 (1.2%)
Lung neoplasm malignant 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Metastases to central nervous system 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Metastatic pain 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Neoplasm malignant 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Neoplasm progression 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Tumour associated fever 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Tumour invasion 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Tumour pain 0/289 (0%) 3/290 (1%) 2/83 (2.4%)
Nervous system disorders
Dizziness 16/289 (5.5%) 4/290 (1.4%) 3/83 (3.6%)
Headache 13/289 (4.5%) 14/290 (4.8%) 9/83 (10.8%)
Ageusia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Amnesia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Aphasia 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Aphonia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Ataxia 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Autonomic nervous system imbalance 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Balance disorder 2/289 (0.7%) 2/290 (0.7%) 0/83 (0%)
Cerebrovascular accident 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Cognitive disorder 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Convulsion 4/289 (1.4%) 0/290 (0%) 3/83 (3.6%)
Coordination abnormal 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Dysaesthesia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Dysarthria 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Dysgeusia 12/289 (4.2%) 5/290 (1.7%) 4/83 (4.8%)
Dyskinesia 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Dystonia 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Encephalopathy 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Epilepsy 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Grand mal convulsion 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hemiparesis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hyperaesthesia 0/289 (0%) 2/290 (0.7%) 1/83 (1.2%)
Hypoaesthesia 3/289 (1%) 0/290 (0%) 0/83 (0%)
Intracranial pressure increased 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Lethargy 3/289 (1%) 0/290 (0%) 0/83 (0%)
Loss of consciousness 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Memory impairment 1/289 (0.3%) 1/290 (0.3%) 1/83 (1.2%)
Monoparesis 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Movement disorder 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Myotonia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Nervous system disorder 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Neuropathy peripheral 2/289 (0.7%) 4/290 (1.4%) 0/83 (0%)
Paraesthesia 5/289 (1.7%) 8/290 (2.8%) 2/83 (2.4%)
Parkinsonism 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Peripheral motor neuropathy 2/289 (0.7%) 0/290 (0%) 1/83 (1.2%)
Peripheral sensory neuropathy 4/289 (1.4%) 0/290 (0%) 0/83 (0%)
Polyneuropathy 1/289 (0.3%) 1/290 (0.3%) 1/83 (1.2%)
Presyncope 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Sciatica 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Somnolence 4/289 (1.4%) 2/290 (0.7%) 1/83 (1.2%)
Speech disorder 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Spinal cord compression 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Syncope 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Toxic encephalopathy 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Transient ischaemic attack 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Tremor 1/289 (0.3%) 0/290 (0%) 2/83 (2.4%)
Vascular encephalopathy 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Vocal cord paralysis 3/289 (1%) 0/290 (0%) 0/83 (0%)
Psychiatric disorders
Anxiety 7/289 (2.4%) 7/290 (2.4%) 6/83 (7.2%)
Depression 10/289 (3.5%) 6/290 (2.1%) 7/83 (8.4%)
Abnormal behaviour 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Affective disorder 0/289 (0%) 2/290 (0.7%) 2/83 (2.4%)
Agitation 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Bradyphrenia 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Confusional state 10/289 (3.5%) 3/290 (1%) 2/83 (2.4%)
Delirium 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Depressed mood 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Dysthymic disorder 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Hallucination 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Insomnia 12/289 (4.2%) 8/290 (2.8%) 3/83 (3.6%)
Mental status changes 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Mood altered 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Restlessness 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Sleep disorder 0/289 (0%) 3/290 (1%) 3/83 (3.6%)
Renal and urinary disorders
Dysuria 5/289 (1.7%) 1/290 (0.3%) 2/83 (2.4%)
Haematuria 2/289 (0.7%) 2/290 (0.7%) 1/83 (1.2%)
Polyuria 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Renal failure 8/289 (2.8%) 1/290 (0.3%) 1/83 (1.2%)
Renal failure acute 4/289 (1.4%) 0/290 (0%) 0/83 (0%)
Urinary hesitation 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Urinary incontinence 6/289 (2.1%) 0/290 (0%) 1/83 (1.2%)
Urinary retention 2/289 (0.7%) 2/290 (0.7%) 2/83 (2.4%)
Reproductive system and breast disorders
Balanitis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Benign prostatic hyperplasia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Genital rash 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Oedema genital 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Scrotal pain 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Vaginal discharge 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 44/289 (15.2%) 51/290 (17.6%) 21/83 (25.3%)
Dyspnoea 54/289 (18.7%) 61/290 (21%) 24/83 (28.9%)
Epistaxis 22/289 (7.6%) 7/290 (2.4%) 2/83 (2.4%)
Haemoptysis 33/289 (11.4%) 32/290 (11%) 8/83 (9.6%)
Atelectasis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Bronchial disorder 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Choking 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Chronic obstructive pulmonary disease 1/289 (0.3%) 2/290 (0.7%) 1/83 (1.2%)
Dysphonia 3/289 (1%) 9/290 (3.1%) 4/83 (4.8%)
Dyspnoea exertional 2/289 (0.7%) 3/290 (1%) 2/83 (2.4%)
Hiccups 1/289 (0.3%) 1/290 (0.3%) 2/83 (2.4%)
Hydropneumothorax 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Hypoventilation 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Hypoxia 2/289 (0.7%) 1/290 (0.3%) 4/83 (4.8%)
Interstitial lung disease 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Lung disorder 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Nasal congestion 3/289 (1%) 0/290 (0%) 0/83 (0%)
Nasal dryness 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Nasal obstruction 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Oesophagobronchial fistula 0/289 (0%) 2/290 (0.7%) 1/83 (1.2%)
Oropharyngeal pain 6/289 (2.1%) 4/290 (1.4%) 0/83 (0%)
Orthopnoea 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Pleural effusion 2/289 (0.7%) 2/290 (0.7%) 1/83 (1.2%)
Pleuritic pain 2/289 (0.7%) 1/290 (0.3%) 0/83 (0%)
Pneumonia aspiration 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pneumonitis 2/289 (0.7%) 1/290 (0.3%) 1/83 (1.2%)
Productive cough 11/289 (3.8%) 9/290 (3.1%) 3/83 (3.6%)
Pulmonary artery thrombosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Pulmonary embolism 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Pulmonary haemorrhage 2/289 (0.7%) 1/290 (0.3%) 1/83 (1.2%)
Pulmonary hypertension 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Pulmonary oedema 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Rales 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Respiratory tract haemorrhage 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Rhinitis allergic 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Rhinorrhoea 6/289 (2.1%) 0/290 (0%) 1/83 (1.2%)
Rhonchi 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Stridor 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Upper-airway cough syndrome 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Wheezing 4/289 (1.4%) 4/290 (1.4%) 2/83 (2.4%)
Skin and subcutaneous tissue disorders
Acne 9/289 (3.1%) 17/290 (5.9%) 6/83 (7.2%)
Dermatitis acneiform 22/289 (7.6%) 14/290 (4.8%) 3/83 (3.6%)
Dry skin 30/289 (10.4%) 24/290 (8.3%) 7/83 (8.4%)
Pruritus 22/289 (7.6%) 31/290 (10.7%) 3/83 (3.6%)
Rash 140/289 (48.4%) 152/290 (52.4%) 33/83 (39.8%)
Alopecia 5/289 (1.7%) 6/290 (2.1%) 1/83 (1.2%)
Blister 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Decubitus ulcer 3/289 (1%) 1/290 (0.3%) 0/83 (0%)
Dermal cyst 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Dermatitis 5/289 (1.7%) 3/290 (1%) 1/83 (1.2%)
Dermatitis allergic 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Dermatitis contact 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Dermatitis exfoliative 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Drug eruption 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Ecchymosis 3/289 (1%) 0/290 (0%) 0/83 (0%)
Eczema 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Erythema 8/289 (2.8%) 5/290 (1.7%) 1/83 (1.2%)
Exfoliative rash 2/289 (0.7%) 6/290 (2.1%) 1/83 (1.2%)
Hair texture abnormal 0/289 (0%) 2/290 (0.7%) 1/83 (1.2%)
Hyperhidrosis 1/289 (0.3%) 2/290 (0.7%) 1/83 (1.2%)
Hyperkeratosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Hypoaesthesia facial 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Ingrowing nail 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Nail bed bleeding 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Nail disorder 10/289 (3.5%) 6/290 (2.1%) 1/83 (1.2%)
Nail toxicity 1/289 (0.3%) 2/290 (0.7%) 0/83 (0%)
Onychalgia 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Onychoclasis 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Onychomadesis 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Palmar erythema 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Palmar-plantar erythrodysaesthesia syndrome 4/289 (1.4%) 3/290 (1%) 3/83 (3.6%)
Petechiae 1/289 (0.3%) 2/290 (0.7%) 0/83 (0%)
Pruritus generalised 0/289 (0%) 3/290 (1%) 1/83 (1.2%)
Purpura 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Rash generalised 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Rash macular 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Rash maculo-papular 7/289 (2.4%) 6/290 (2.1%) 3/83 (3.6%)
Rash papular 3/289 (1%) 2/290 (0.7%) 0/83 (0%)
Rash pruritic 1/289 (0.3%) 4/290 (1.4%) 0/83 (0%)
Scar pain 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Skin disorder 3/289 (1%) 1/290 (0.3%) 1/83 (1.2%)
Skin exfoliation 5/289 (1.7%) 1/290 (0.3%) 0/83 (0%)
Skin fissures 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Skin haemorrhage 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Skin irritation 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Skin lesion 2/289 (0.7%) 2/290 (0.7%) 1/83 (1.2%)
Skin mass 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Skin plaque 1/289 (0.3%) 0/290 (0%) 0/83 (0%)
Skin reaction 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Skin toxicity 11/289 (3.8%) 9/290 (3.1%) 2/83 (2.4%)
Skin ulcer 4/289 (1.4%) 1/290 (0.3%) 0/83 (0%)
Urticaria 0/289 (0%) 2/290 (0.7%) 0/83 (0%)
Xeroderma 1/289 (0.3%) 1/290 (0.3%) 0/83 (0%)
Surgical and medical procedures
Haemorrhage 0/289 (0%) 1/290 (0.3%) 1/83 (1.2%)
Vascular disorders
Flushing 0/289 (0%) 0/290 (0%) 1/83 (1.2%)
Hot flush 3/289 (1%) 0/290 (0%) 0/83 (0%)
Hypertension 10/289 (3.5%) 3/290 (1%) 2/83 (2.4%)
Hypotension 13/289 (4.5%) 7/290 (2.4%) 2/83 (2.4%)
Orthostatic hypotension 4/289 (1.4%) 0/290 (0%) 0/83 (0%)
Phlebitis 2/289 (0.7%) 0/290 (0%) 0/83 (0%)
Subclavian artery stenosis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Subclavian vein thrombosis 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Superior vena cava syndrome 0/289 (0%) 1/290 (0.3%) 0/83 (0%)
Thrombosis 1/289 (0.3%) 0/290 (0%) 1/83 (1.2%)
Venous thrombosis 1/289 (0.3%) 0/290 (0%) 0/83 (0%)

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:
NCT00673049
Other Study ID Numbers:
  • A4021018
First Posted:
May 7, 2008
Last Update Posted:
Jul 24, 2013
Last Verified:
Jul 1, 2013