Trial Outcomes & Findings for Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study) (NCT NCT00778830)

NCT ID: NCT00778830

Last Updated: 2015-05-14

Results Overview

Response rate was defined as the percentage of subjects with BORR (confirmed complete response \[CR\] or partial response \[PR\]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 289 participants
• Primary outcome timeframe: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012)
• Results posted on: 2015-05-14

Participant Flow

First/Last subject (informed consent): February 2009/June 2012. Study completion date: April 2014. Clinical data cut-off: 31 March 2014. Subjects were recruited in 12 countries (Australia, China, Hong Kong, India, Indonesia, Korea, Malaysia, Singapore, Pakistan, Philippines, Taiwan and Thailand) across the globe in 43 centers.

Enrolled: 661 screened for eligibility; 372 were excluded (mainly non-fulfillment of inclusion or exclusion criteria). 289 subjects were assigned to the treatment groups.

Participant milestones

Measure	Cetuximab Plus FOLFIRI Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m\^2 ,folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab Plus FOLFOX Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m\^2, folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Overall Study STARTED	101	188
Overall Study COMPLETED	101	187
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Cetuximab Plus FOLFIRI Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m\^2 ,folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab Plus FOLFOX Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m\^2, folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Overall Study Ongoing at data cut-off	0	1

Baseline Characteristics

Study Evaluating the Safety and Efficacy of FOLFIRI Plus Cetuximab or FOLFOX Plus Cetuximab as First-line Therapy in Subjects With KRAS Wild-type Metastatic Colorectal Cancer (APEC-Study)

Baseline characteristics by cohort

Measure	Cetuximab Plus FOLFIRI n=101 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m\^2 ,folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab Plus FOLFOX n=188 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m\^2, folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Total n=289 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	70 Participants n=93 Participants	145 Participants n=4 Participants	215 Participants n=27 Participants
Age, Categorical >=65 years	31 Participants n=93 Participants	43 Participants n=4 Participants	74 Participants n=27 Participants
Sex: Female, Male Female	35 Participants n=93 Participants	69 Participants n=4 Participants	104 Participants n=27 Participants
Sex: Female, Male Male	66 Participants n=93 Participants	119 Participants n=4 Participants	185 Participants n=27 Participants

PRIMARY outcome

Timeframe: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited until data cut-off date (31 May 2012)

Population: Intention-to-treat (ITT) population consisted of all the enrolled subjects who received at least one dose of study treatment.

Response rate was defined as the percentage of subjects with BORR (confirmed complete response [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks.

Outcome measures

Measure	Cetuximab Plus FOLFIRI n=101 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m\^2 ,folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab Plus FOLFOX n=188 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m\^2, folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Percentage of Subjects With Best Overall Confirmed Response Rate (BORR)	54.5 Percentage of subjects	61.2 Percentage of subjects

SECONDARY outcome

Timeframe: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)

Population: The ITT population consisted of all the enrolled subjects who received at least one dose of study treatment.

PFS time was defined as the time from first administration of study drug until first observation of disease progression or death when death occurs within 90 days of the last tumor assessment or first study drug dose whichever occurred.

Outcome measures

Measure	Cetuximab Plus FOLFIRI n=101 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m\^2 ,folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab Plus FOLFOX n=188 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m\^2, folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Progression-Free Survival (PFS) Time	11.1 months Interval 8.1 to 14.8	11.1 months Interval 9.0 to 12.7

SECONDARY outcome

Timeframe: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)

Population: The ITT population consisted of all the enrolled subjects who received at least one dose of study treatment.

OS time was defined as the time from first administration of study drug until date of death, assessed up to 5 years. OS time was censored if the subject was found to be alive on the last date of the assessment.

Outcome measures

Measure	Cetuximab Plus FOLFIRI n=101 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m\^2 ,folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab Plus FOLFOX n=188 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m\^2, folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Overall Survival (OS) Time	26.6 months Interval 21.5 to 33.8	27.0 months Interval 22.8 to 30.1

SECONDARY outcome

Timeframe: From the start of the trial until disease progression, death or last tumor assessment, reported between day of first subject recruited and until data cut-off date (31 March 2014)

Population: Safety population consisted of all the enrolled subjects who received at least one dose of study treatment.

An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Measure	Cetuximab Plus FOLFIRI n=101 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfiri (Irinotecan administered intravenously at a dose of 180 mg/m\^2 ,folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.	Cetuximab Plus FOLFOX n=188 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly followed by Folfox (Oxaliplatin administered intravenously at a dose of 180 mg/m\^2, folinic acid administered intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form), 5-fluorouracil administered intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion at a dose of 2,400 mg/m\^2) on Day 1 of 14 days treatment cycle until disease progression, occurrence of unacceptable toxicity, or withdrawal of consent.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs	99 Subjects	180 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death Treatment Emergent SAEs	37 Subjects	64 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs Leading to Death	5 Subjects	10 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs Leading to Discontinuation	0 Subjects	0 Subjects

Adverse Events

Cetuximab Plus FOLFIRI

Serious events: 37 serious events

Other events: 93 other events

Deaths: 0 deaths

Cetuximab Plus FOLFOX

Serious events: 64 serious events

Other events: 177 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cetuximab Plus FOLFIRI n=101 participants at risk Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly until disease progression, death, or consent withdrawal. Irinotecan was administered intravenously at a dose of 180 mg/m\^2 along with folinic acid intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form) and 5-fluorouracil at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m\^2 given biweekly until disease progression, death, or consent withdrawal.	Cetuximab Plus FOLFOX n=188 participants at risk Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly until disease progression, death, or consent withdrawal. Oxaliplatin was administered intravenously at a dose of 100 mg/m\^2 along with folinic acid intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form) and 5-fluorouracil at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m\^2 given biweekly until disease progression, death, or consent withdrawal.
Blood and lymphatic system disorders Anaemia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Blood and lymphatic system disorders Febrile neutropenia	2.0% 2/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	3.2% 6/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Blood and lymphatic system disorders Iron deficiency anaemia	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Blood and lymphatic system disorders Neutropenia	4.0% 4/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.6% 3/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Cardiac disorders Cardiopulmonary failure	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Cardiac disorders Myocardial infarction	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Cardiac disorders Palpitations	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Cardiac disorders Supraventricular tachycardia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Eye disorders Vision blurred	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Abdominal pain	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.6% 3/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Constipation	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Diarrhoea	4.0% 4/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	3.2% 6/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Gastritis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Haematochezia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Ileus	3.0% 3/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Intestinal obstruction	5.0% 5/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Nausea	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Rectal Haemorrhage	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Rectal obstruction	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Small intestinal haemorrhage	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Stomatitis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Vomiting	2.0% 2/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	2.1% 4/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Chest discomfort	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Death	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Disease progression	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Fatigue	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Multi-organ failure	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Pyrexia	3.0% 3/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	3.7% 7/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Hepatobiliary disorders Cholecystitis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Immune system disorders Drug hypersensitivity	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.6% 3/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Bacteraemia	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Biliary sepsis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Bronchitis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Bronchopneumonia	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Catheter site infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.6% 3/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Cellulitis	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Device related infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Escherichia urinary tract infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Gastroenteritis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Herpes zoster	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Infection	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Klebsiella sepsis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Lower respiratory tract infection	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Mycobacterium abscessus infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Nail infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Onychomycosis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Paronychia	2.0% 2/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Pneumonia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.6% 3/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Pneumonia klebsiella	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Pneumonia viral	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Sepsis	2.0% 2/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Septic shock	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Skin infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Staphylococcal infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Upper respiratory tract infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Urinary tract infection	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Wound infection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Injury, poisoning and procedural complications Contusion	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Injury, poisoning and procedural complications Overdose	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Investigations Blood bilirubin increased	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Investigations Blood creatinine increased	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Acidosis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Dehydration	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.6% 3/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Diabetic ketoacidosis	2.0% 2/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hypokalaemia	3.0% 3/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	2.1% 4/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hypomagnesaemia	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hypophosphataemia	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Musculoskeletal and connective tissue disorders Back pain	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Musculoskeletal and connective tissue disorders Bone pain	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor perforation	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Convulsion	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Dizziness	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Psychiatric disorders Confusional state	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Renal and urinary disorders Haematuria	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Renal and urinary disorders Hydronephrosis	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Renal and urinary disorders Proteinuria	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Renal and urinary disorders Renal failure acute	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Reproductive system and breast disorders Pelvic fluid collection	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Dysaesthesia pharynx	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.6% 3/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Acne	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Vascular disorders Deep vein thrombosis	3.0% 3/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Vascular disorders Hypotension	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Vascular disorders Jugular vein thrombosis	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.53% 1/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Vascular disorders Vena cava thrombosis	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Vascular disorders Venous thrombosis	2.0% 2/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	0.00% 0/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Paraesthesia	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	1.1% 2/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Other adverse events

Measure	Cetuximab Plus FOLFIRI n=101 participants at risk Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly until disease progression, death, or consent withdrawal. Irinotecan was administered intravenously at a dose of 180 mg/m\^2 along with folinic acid intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form) and 5-fluorouracil at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m\^2 given biweekly until disease progression, death, or consent withdrawal.	Cetuximab Plus FOLFOX n=188 participants at risk Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) biweekly until disease progression, death, or consent withdrawal. Oxaliplatin was administered intravenously at a dose of 100 mg/m\^2 along with folinic acid intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form) and 5-fluorouracil at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m\^2 given biweekly until disease progression, death, or consent withdrawal.
Blood and lymphatic system disorders Neutropenia	52.5% 53/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	53.2% 100/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Blood and lymphatic system disorders Leukopenia	23.8% 24/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	14.9% 28/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Blood and lymphatic system disorders Anaemia	13.9% 14/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	6.9% 13/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Blood and lymphatic system disorders Thrombocytopenia	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	23.4% 44/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Cardiac disorders Cardiac disorders	9.9% 10/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	4.3% 8/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Eye disorders Eye disorders	8.9% 9/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	10.6% 20/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Nausea	60.4% 61/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	36.2% 68/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Diarrhoea	57.4% 58/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	42.0% 79/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Vomiting	36.6% 37/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	33.5% 63/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Stomatitis	30.7% 31/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	27.7% 52/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Constipation	21.8% 22/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	22.3% 42/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Abdominal pain	19.8% 20/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	7.4% 14/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Mouth ulceration	9.9% 10/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	10.1% 19/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Dyspepsia	9.9% 10/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	5.3% 10/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Abdominal pain upper	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	6.4% 12/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Abdominal distension	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	2.7% 5/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	2.7% 5/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Fatigue	20.8% 21/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	25.5% 48/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Pyrexia	16.8% 17/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	18.1% 34/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Mucosal inflammation	14.9% 15/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	28.7% 54/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
General disorders Asthenia	6.9% 7/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	7.4% 14/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Hepatobiliary disorders Hepatic function abnormal	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	4.8% 9/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Immune system disorders Drug hypersensitivity	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	9.0% 17/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Paronychia	31.7% 32/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	25.5% 48/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Upper respiratory tract infection	10.9% 11/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	7.4% 14/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Conjunctivitis	5.0% 5/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	10.1% 19/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Infections and infestations Nasopharyngitis	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	5.9% 11/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	8.9% 9/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	8.0% 15/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Investigations Weight decreased	8.9% 9/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	5.3% 10/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Investigations Alanine aminotransferase increased	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	7.4% 14/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Investigations Aspartate aminotransferase increased	3.0% 3/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	7.4% 14/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Investigations Platelet count decreased	0.00% 0/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	5.3% 10/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Decreased appetite	32.7% 33/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	27.1% 51/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hypokalaemia	20.8% 21/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	15.4% 29/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hypocalcaemia	7.9% 8/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	3.7% 7/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Metabolism and nutrition disorders Hypomagnesaemia	6.9% 7/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	16.5% 31/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Musculoskeletal and connective tissue disorders Back pain	6.9% 7/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	4.3% 8/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Dizziness	8.9% 9/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	12.2% 23/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Headache	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	7.4% 14/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Dysgeusia	5.9% 6/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	6.9% 13/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Neuropathy peripheral	4.0% 4/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	33.5% 63/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders Hypoaesthesia	3.0% 3/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	7.4% 14/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Nervous system disorders peripheral sensory neuropathy	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	18.1% 34/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Psychiatric disorders Insomnia	12.9% 13/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	10.6% 20/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Renal and urinary disorders Renal and urinary disorders	6.9% 7/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	5.9% 11/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Cough	15.8% 16/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	12.2% 23/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 8/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	8.0% 15/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Hiccups	6.9% 7/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	3.2% 6/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 2/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	9.0% 17/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Rash	54.5% 55/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	61.2% 115/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Alopecia	29.7% 30/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	9.0% 17/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Dry skin	16.8% 17/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	15.4% 29/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Pruritus	15.8% 16/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	12.8% 24/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Acne	15.8% 16/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	11.7% 22/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Dermatitis acneiform	11.9% 12/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	11.2% 21/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	10.9% 11/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	16.0% 30/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Skin and subcutaneous tissue disorders Skin fissures	10.9% 11/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	5.9% 11/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Vascular disorders Phlebitis	0.99% 1/101 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	5.9% 11/188 • From the start of the trial treatment up to the data cut-off date (31 March 2014) A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Additional Information

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