Trial Outcomes & Findings for Trial Of CP-751, 871 And Erlotinib In Refractory Lung Cancer (NCT NCT00673049)

Last Updated: 2013-07-24

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

583 participants

Primary outcome timeframe

Baseline, assessed every cycle until disease progression and then every 4 weeks until death, up to 30.65 months

Results posted on

2013-07-24

Participant Flow

Participant milestones

Participant milestones
Measure	Figitumumab + Erlotinib (Randomized to and Treated With) 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 (Randomized to and Treated With) Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.	Randomized to Figi + Erlo Arm But Treated Only With Erlo Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.	Erlotinib, Then Figitumumab 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.
Before Progression on Erlotinib STARTED	292	290	1	0
Before Progression on Erlotinib Treated	289	289	1	0
Before Progression on Erlotinib COMPLETED	0	0	0	0
Before Progression on Erlotinib NOT COMPLETED	292	290	1	0
After Progression on Erlotinib STARTED	0	0	0	83
After Progression on Erlotinib COMPLETED	0	0	0	0
After Progression on Erlotinib NOT COMPLETED	0	0	0	83

Reasons for withdrawal

Reasons for withdrawal
Measure	Figitumumab + Erlotinib (Randomized to and Treated With) 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 (Randomized to and Treated With) Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.	Randomized to Figi + Erlo Arm But Treated Only With Erlo Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.	Erlotinib, Then Figitumumab 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.
Before Progression on Erlotinib Randomized but not treated	3	1	0	0
Before Progression on Erlotinib Death	235	167	1	0
Before Progression on Erlotinib Lost to Follow-up	9	5	0	0
Before Progression on Erlotinib Withdrawal by Subject	26	18	0	0
Before Progression on Erlotinib Other	1	2	0	0
Before Progression on Erlotinib study terminated by sponsor	18	14	0	0
Before Progression on Erlotinib Switched to figitumumab	0	83	0	0
After Progression on Erlotinib Death	0	0	0	71
After Progression on Erlotinib Lost to Follow-up	0	0	0	3
After Progression on Erlotinib Withdrawal by Subject	0	0	0	5
After Progression on Erlotinib study terminated by sponsor	0	0	0	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Figitumumab + Erlotinib (as Randomized) n=293 Participants 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 (as Randomized) n=290 Participants 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 n=583 Participants Total of all reporting groups
Age, Customized <70 years	226 participants n=5 Participants	222 participants n=7 Participants	448 participants n=5 Participants
Age, Customized >=70 years	67 participants n=5 Participants	68 participants n=7 Participants	135 participants n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	65 Participants n=7 Participants	130 Participants n=5 Participants
Sex: Female, Male Male	228 Participants n=5 Participants	225 Participants n=7 Participants	453 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, assessed every cycle until disease progression and then every 4 weeks until death, up to 30.65 months

Population: Full (intent-to-treat) analysis set, which included all participants randomized regardless of treatment received.

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.

Outcome measures

Outcome measures
Measure	Figitumumab + Erlotinib n=293 Participants 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 n=290 Participants Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Overall Survival	5.7 months Interval 4.8 to 6.7	6.2 months Interval 5.8 to 7.2

SECONDARY outcome

Timeframe: 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

Population: Full (intent-to-treat) analysis set, which included all participants randomized regardless of treatment received.

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.

Outcome measures

Outcome measures
Measure	Figitumumab + Erlotinib n=293 Participants 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 n=290 Participants Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Progression Free Survival (PFS)	2.1 months Interval 1.9 to 2.6	2.6 months Interval 2.1 to 2.8

SECONDARY outcome

Population: Full (intent-to-treat) analysis set, which included all participants randomized regardless of treatment received.

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.

Outcome measures

Outcome measures
Measure	Figitumumab + Erlotinib n=293 Participants 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 n=290 Participants Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Percentage of Participants With Objective Response	5.5 percentage of participants Interval 3.2 to 8.7	3.8 percentage of participants Interval 1.9 to 6.7

SECONDARY outcome

Timeframe: 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

Population: Due to futility, the study was terminated early; therefore pharmacokinetic data were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Due to futility, the study was terminated early; therefore pharmacokinetic data were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Population: 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.

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

Outcome measures

Outcome measures
Measure	Figitumumab + Erlotinib n=360 Participants 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 Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.
Percentage of Participants Reporting Positive for Total Anti-drug Antibodies (ADA)	0.28 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, Cycle 2 Day 1 (predose) and EOT (21-28 days after last dose)

Population: Due to futility, the study was terminated early; therefore biomarker results were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every other cycle and EOT (21-28 days after last dose)

Population: Due to futility, the study was terminated early; therefore EQ-5D data were not analyzed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: 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).

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Figitumumab + Erlotinib

Serious events: 204 serious events

Other events: 265 other events

Deaths: 0 deaths

Erlotinib

Serious events: 153 serious events

Other events: 265 other events

Deaths: 0 deaths

Erlotinib, Then Figitumumab

Serious events: 63 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Figitumumab + Erlotinib n=289 participants at risk 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 n=290 participants at risk Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.	Erlotinib, Then Figitumumab n=83 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.4% 4/289 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.	2.1% 6/290 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.	2.4% 2/83 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.
Infections and infestations Lower respiratory tract infection	1.4% 4/289 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.	0.00% 0/290 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.	1.2% 1/83 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.
General disorders Pyrexia	1.4% 4/289 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.	1.7% 5/290 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.	1.2% 1/83 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.
Infections and infestations Respiratory tract infection	1.4% 4/289 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.	1.0% 3/290 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.	0.00% 0/83 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.
Gastrointestinal disorders Vomiting	1.4% 4/289 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.	1.0% 3/290 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.	1.2% 1/83 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.
Blood and lymphatic system disorders Anaemia	1.0% 3/289 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.	1.0% 3/290 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.	2.4% 2/83 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.
Gastrointestinal disorders Large intestine perforation	0.00% 0/289 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.	0.00% 0/290 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.	1.2% 1/83 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.
General disorders General physical health deterioration	1.0% 3/289 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.	1.7% 5/290 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.	6.0% 5/83 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.
General disorders Pain	1.0% 3/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.0% 3/289 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.	1.0% 3/290 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.	1.2% 1/83 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.
Gastrointestinal disorders Abdominal pain	0.69% 2/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Cardiac disorders Cardiac failure	0.69% 2/289 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.	0.00% 0/290 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.	1.2% 1/83 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.
Nervous system disorders Cerebrovascular accident	0.69% 2/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
General disorders Death	0.35% 1/289 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.	0.00% 0/290 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.	1.2% 1/83 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.
Gastrointestinal disorders Dysphagia	0.69% 2/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
General disorders Fatigue	0.69% 2/289 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.	0.34% 1/290 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.	1.2% 1/83 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.
Infections and infestations Gastroenteritis	0.69% 2/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.69% 2/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.69% 2/289 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.	1.4% 4/290 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.	1.2% 1/83 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.69% 2/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.69% 2/289 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.	1.0% 3/290 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.	1.2% 1/83 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.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.69% 2/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Renal and urinary disorders Renal failure	0.69% 2/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Renal and urinary disorders Renal failure acute	0.69% 2/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.69% 2/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Infections and infestations Sepsis	0.69% 2/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Alveolitis allergic	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Cardiac disorders Arrhythmia	0.35% 1/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Metabolism and nutrition disorders Malnutrition	0.00% 0/289 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.	0.00% 0/290 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.	1.2% 1/83 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.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Respiratory, thoracic and mediastinal disorders Aspiration	0.35% 1/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Infections and infestations Bacteraemia	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Investigations Band neutrophil count increased	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Investigations Blood creatinine increased	0.35% 1/289 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.	0.00% 0/290 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.	1.2% 1/83 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.
Infections and infestations Bronchopneumonia	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.
Cardiac disorders Cardiac arrest	0.35% 1/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
General disorders Chills	0.35% 1/289 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.	0.00% 0/290 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.	0.00% 0/83 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.

Other adverse events
Measure	Figitumumab + Erlotinib n=289 participants at risk 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 n=290 participants at risk Erlotinib was taken as 150 mg daily at least 1 hour before or 2 hours after the ingestion of food.	Erlotinib, Then Figitumumab n=83 participants at risk 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.
Blood and lymphatic system disorders Anaemia	9.7% 28/289 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.	9.0% 26/290 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.	13.3% 11/83 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.
Gastrointestinal disorders Abdominal pain upper	2.8% 8/289 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.	2.8% 8/290 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.	6.0% 5/83 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.
Gastrointestinal disorders Constipation	5.9% 17/289 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.	6.6% 19/290 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.	10.8% 9/83 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.
Gastrointestinal disorders Diarrhoea	42.6% 123/289 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.	36.6% 106/290 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.	12.0% 10/83 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.
Gastrointestinal disorders Dysphagia	4.8% 14/289 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.	3.8% 11/290 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.	7.2% 6/83 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.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/289 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.	0.34% 1/290 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.	0.00% 0/83 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.
Gastrointestinal disorders Mouth ulceration	5.5% 16/289 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.	1.4% 4/290 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.	1.2% 1/83 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.
Gastrointestinal disorders Nausea	18.7% 54/289 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.	12.4% 36/290 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.	9.6% 8/83 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.
Gastrointestinal disorders Stomatitis	6.2% 18/289 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.	2.1% 6/290 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.	0.00% 0/83 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.
Gastrointestinal disorders Vomiting	17.0% 49/289 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.	7.9% 23/290 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.	8.4% 7/83 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.
Blood and lymphatic system disorders Leukocytosis	0.69% 2/289 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.	0.34% 1/290 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.	2.4% 2/83 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.
General disorders Asthenia	27.3% 79/289 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.	15.9% 46/290 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.	30.1% 25/83 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.
General disorders Chest pain	10.7% 31/289 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.	9.7% 28/290 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.	25.3% 21/83 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.
General disorders Fatigue	22.5% 65/289 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.	18.3% 53/290 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.	19.3% 16/83 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.
General disorders Mucosal inflammation	11.4% 33/289 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.	3.8% 11/290 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.	0.00% 0/83 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.
General disorders Oedema peripheral	2.8% 8/289 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.	5.5% 16/290 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.	1.2% 1/83 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.
General disorders Pyrexia	8.7% 25/289 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.	6.2% 18/290 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.	6.0% 5/83 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.
Infections and infestations Paronychia	5.9% 17/289 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.	2.8% 8/290 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.	1.2% 1/83 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.
Investigations Weight decreased	22.5% 65/289 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.	11.4% 33/290 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.	22.9% 19/83 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.
Metabolism and nutrition disorders Decreased appetite	39.8% 115/289 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.	24.1% 70/290 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.	38.6% 32/83 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.
Metabolism and nutrition disorders Dehydration	7.3% 21/289 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.	2.1% 6/290 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.	2.4% 2/83 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.
Metabolism and nutrition disorders Hyperglycaemia	12.8% 37/289 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.	4.5% 13/290 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.	14.5% 12/83 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.
Blood and lymphatic system disorders Leukopenia	1.4% 4/289 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.	0.69% 2/290 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.	0.00% 0/83 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.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 11/289 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.	3.8% 11/290 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.	6.0% 5/83 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.
Musculoskeletal and connective tissue disorders Back pain	6.6% 19/289 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.	8.6% 25/290 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.	10.8% 9/83 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.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.4% 7/289 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.	1.7% 5/290 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.	7.2% 6/83 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.4% 7/289 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.	3.1% 9/290 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.	8.4% 7/83 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.
Musculoskeletal and connective tissue disorders Pain in extremity	5.2% 15/289 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.	1.7% 5/290 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.	1.2% 1/83 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.
Nervous system disorders Dizziness	5.5% 16/289 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.	1.4% 4/290 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.	3.6% 3/83 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.
Nervous system disorders Headache	4.5% 13/289 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.	4.8% 14/290 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.	10.8% 9/83 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.
Psychiatric disorders Anxiety	2.4% 7/289 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.	2.4% 7/290 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.	7.2% 6/83 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.
Psychiatric disorders Depression	3.5% 10/289 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.	2.1% 6/290 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.	8.4% 7/83 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.
Respiratory, thoracic and mediastinal disorders Cough	15.2% 44/289 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.	17.6% 51/290 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.	25.3% 21/83 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.7% 54/289 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.	21.0% 61/290 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.	28.9% 24/83 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.6% 22/289 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.	2.4% 7/290 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.	2.4% 2/83 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.
Respiratory, thoracic and mediastinal disorders Haemoptysis	11.4% 33/289 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.	11.0% 32/290 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.	9.6% 8/83 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.
Skin and subcutaneous tissue disorders Acne	3.1% 9/289 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.	5.9% 17/290 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.	7.2% 6/83 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.
Skin and subcutaneous tissue disorders Dermatitis acneiform	7.6% 22/289 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.	4.8% 14/290 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.	3.6% 3/83 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.
Skin and subcutaneous tissue disorders Dry skin	10.4% 30/289 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.	8.3% 24/290 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.	8.4% 7/83 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.
Skin and subcutaneous tissue disorders Pruritus	7.6% 22/289 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.	10.7% 31/290 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.	3.6% 3/83 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.