Trial Outcomes & Findings for Study Using CP-751,871 In Patients With Stage IV Colorectal Cancer That Has Not Responded To Previous Anti-Cancer Treatments (NCT NCT00560560)

Last Updated: 2013-05-20

Results Overview

The 6 month survival probability was defined as the probability of survival at 6 months based on the Kaplan-Meier estimate. The time was from date of enrollment to date of death due to any cause. For participants who were last known to be alive, overall survival was censored at the last contact date.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

168 participants

Primary outcome timeframe

Baseline up to Month 6

Results posted on

2013-05-20

Participant Flow

Participant milestones

Participant milestones
Measure	Figitumumab 20 mg/kg Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Overall Study STARTED	85	83
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	85	83

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Using CP-751,871 In Patients With Stage IV Colorectal Cancer That Has Not Responded To Previous Anti-Cancer Treatments

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Figitumumab 20 mg/kg n=85 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Total n=168 Participants Total of all reporting groups
Age, Customized <65 years	56 participants n=5 Participants	59 participants n=7 Participants	115 participants n=5 Participants
Age, Customized >=65 years	29 participants n=5 Participants	24 participants n=7 Participants	53 participants n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	35 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	48 Participants n=7 Participants	94 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Month 6

Population: All enrolled participants.

Outcome measures

Outcome measures
Measure	Figitumumab 20 mg/kg n=85 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Estimate of the 6 Month Survival Probability	49.4 Percent chance of survival Interval 38.8 to 60.0	44.1 Percent chance of survival Interval 33.4 to 54.9

SECONDARY outcome

Timeframe: From date of enrollment until death or censorship, up to 33 months

Population: All enrolled participants.

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

Outcome measures

Outcome measures
Measure	Figitumumab 20 mg/kg n=85 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Overall Survival	5.8 Months Interval 4.3 to 7.1	5.6 Months Interval 4.1 to 6.9

SECONDARY outcome

Timeframe: Baseline until tumor progression or censorship, up to 33 months. The frequency of tumor assessments was screening, every cycle, end of treatment (within 28 days of last dose of study drug), and follow-up.

Population: All enrolled participants.

The period from study entry until disease progression. Participants without progression or death were censored at time of last disease assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as 20% increase in the sum of longest diameters of target measurable lesions, or a clear increase in a non-target lesion, or the apprearance of new lesions.

Outcome measures

Outcome measures
Measure	Figitumumab 20 mg/kg n=85 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Progression-Free Survival (PFS)	1.4 months Interval 1.3 to 1.8	1.4 months Interval 1.3 to 1.7

SECONDARY outcome

Timeframe: Baseline, every cycle (Day 15-21 or according to local standard), end of treatment (within 28 days of last dose of study drug) and follow-up (150 days after last dose of study drug), up to 33 months

Population: Per protocol. All enrolled participants who started treatment, with measurable disease and adequate baseline assessment.

Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target and non-target disease. PR applied only to participants with at least one measurable lesion. Greater than or equal to 30 % decrease under baseline of the sum of longest diameters of all target measurable lesions.

Outcome measures

Outcome measures
Measure	Figitumumab 20 mg/kg n=75 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=81 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Percentage of Participants With Objective Response	0 Percentage of participants Interval 0.0 to 4.8	0 Percentage of participants Interval 0.0 to 4.5

SECONDARY outcome

Timeframe: Pre-dose on Day 1, 1 hour after end of infusion (post-dose) on Day 2 in Cycle 1, pre-dose on Day 1 in Cycles 2,3,4, 1 hour post-dose on Day 1 in Cycle 5

Population: All participants for whom PK was assessed at least once. The numbers of participants analyzed are numbers of observation (non-missing concentrations). The numbers for 20 mg/kg group are 84,7,3,2,13 for five cycles, respectively. The numbers for 30 mg/kg group are 79,8,2,2,8 for five cycles, respectively.

The measurement of mean plasma concentration of figitumumab in Day 1 of Cycle 1,2,3,4,5

Outcome measures

Outcome measures
Measure	Figitumumab 20 mg/kg n=85 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Descriptive Summary of Figitumumab Concentration Versus Time Cycle1/Day2	647.0 miligrams/liter (mg/L) Standard Deviation 288.23	877.7 miligrams/liter (mg/L) Standard Deviation 230.22
Descriptive Summary of Figitumumab Concentration Versus Time Cycle2/Day1	244.0 miligrams/liter (mg/L) Standard Deviation 114.00	221.0 miligrams/liter (mg/L) Standard Deviation 119.65
Descriptive Summary of Figitumumab Concentration Versus Time Cycle3/Day1	255.7 miligrams/liter (mg/L) Standard Deviation 60.476	245.0 miligrams/liter (mg/L) Standard Deviation 19.799
Descriptive Summary of Figitumumab Concentration Versus Time Cycle4/Day1	76.30 miligrams/liter (mg/L) Standard Deviation 1.2728	427.0 miligrams/liter (mg/L) Standard Deviation 86.267
Descriptive Summary of Figitumumab Concentration Versus Time CYcle5/Day1	756.2 miligrams/liter (mg/L) Standard Deviation 239.08	745.5 miligrams/liter (mg/L) Standard Deviation 216.14

SECONDARY outcome

Timeframe: Up to 2 hours prior to infusion in Cycles 1 and 4, at the end of treatment, and at the 4th scheduled follow-up visit (~150 days after the last infusion)

Population: Participants for whom at least one ADA measurement was done. The outcome was not analyzed and only listing of ADA level for each participant was available.

The immunogenicity of figitumumab in terms of producing an antidrug antibody (ADA) response were monitored.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 pre-dosing and Cycle 4 pre-dosing

Population: All enrolled participants who started treatment and who have at least one sample submitted. The total number of participants for this outcome measure was less than the original population. "N" means the numbers of units analyzed in Pre-treatment and/or Baseline, and Post-Baseline and/or Follow-up, respectively.

The quantification of circulating tumor cells (CTCs) expressing the IGF-1R in this patient population. Blood samples were collected, and were measured using an automated microscope system.

Outcome measures

Outcome measures
Measure	Figitumumab 20 mg/kg n=85 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R) Pre-treatment and/or baseline (n=44,71)	2.02 number of CTC expressing IGF-1R/ml blood Standard Deviation 8.79	0.54 number of CTC expressing IGF-1R/ml blood Standard Deviation 1.29
Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R) Post-Baseline and/or follow-up (n=18,17)	0.22 number of CTC expressing IGF-1R/ml blood Standard Deviation 0.55	0.00 number of CTC expressing IGF-1R/ml blood Standard Deviation 0.00

SECONDARY outcome

Timeframe: Cycle 1 pre-dosing and Cycle 4 pre-dosing

The quantification of circulating tumor cells (CTCs)in this patient population. Blood samples were collected, and were measured using an automated microscope system.

Outcome measures

Outcome measures
Measure	Figitumumab 20 mg/kg n=85 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 Participants Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Counts of Circulating Tumor Cells (CTCs) Pre-treatment and/or baseline (n=44,71)	7.25 Number of CTC/ml of blood Standard Deviation 16.59	4.90 Number of CTC/ml of blood Standard Deviation 9.83
Counts of Circulating Tumor Cells (CTCs) Post-Baseline and/or follow-up (n=19,17)	1.26 Number of CTC/ml of blood Standard Deviation 1.94	2.18 Number of CTC/ml of blood Standard Deviation 7.06

Adverse Events

Figitumumab 20 mg/kg

Serious events: 56 serious events

Other events: 85 other events

Deaths: 0 deaths

Figitumumab 30 mg/kg

Serious events: 53 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Serious adverse events
Measure	Figitumumab 20 mg/kg n=85 participants at risk Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 participants at risk Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Blood and lymphatic system disorders Anaemia	3.5% 3/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	4.7% 4/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 4/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Proctalgia	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Small intestinal obstruction	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 4/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Deafness bilateral	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ascites	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal perforation	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Disease progression	57.6% 49/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	51.8% 43/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders General physical health deterioration	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.6% 3/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Malaise	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Ulcer	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholecystitis	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic pain	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infection	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Klebsiella bacteraemia	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	3.5% 3/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Abdominal sepsis	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Bacteraemia	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Escherichia infection	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Spinal cord injury cauda equina	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fracture	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.6% 3/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetes mellitus	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Figitumumab 20 mg/kg n=85 participants at risk Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.	Figitumumab 30 mg/kg n=83 participants at risk Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter.
Musculoskeletal and connective tissue disorders Muscular weakness	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.2% 7/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.6% 3/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	10.6% 9/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.2% 6/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	4.7% 4/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.6% 3/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachycardia	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Cerumen impaction	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Deafness	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Hypoacusis	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Tinnitus	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Deafness bilateral	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Deafness unilateral	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear pain	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Motion sickness	0.00% 0/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	16.5% 14/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.3% 11/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain lower	4.7% 4/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 2/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	9.4% 8/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.4% 7/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Anal inflammation	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Cheilitis	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	20.0% 17/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	17.6% 15/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	30.1% 25/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.2% 6/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dysphagia	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Faeces discoloured	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Flatulence	2.4% 2/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal disorder	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gingivitis	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Glossodynia	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal obstruction	3.5% 3/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Mucous stools	1.2% 1/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	27.1% 23/85 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	32.5% 27/83 • Includes date up to 150 days after last dose of study drug The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.