A Study of Necitumumab in the First-Line Treatment of Sta... | NCT01763788

ID	Type	Description	Link
I4X-JE-JFCM	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Necitumumab + Gem and Cis	Experimental	Phase 1b Dose Escalation: Necitumumab 800 milligram (mg) on Days 1 and 8 of every 21 day cycle, administered as an intravenous (IV) infusion. Gemcitabine (Gem) dose escalation of 1000 or 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles. Cisplatin (Cis) 75 mg/m^2 on Day 1 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles. Phase 2 Randomized: Necitumumab 800 mg on Days 1 and 8 of every 21 day cycle, administered as an IV infusion. Gemcitabine at fixed dose determined in Phase 1b (1000 or 1250 mg/m^2) on Days 1 and 8 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles. Cisplatin 75 mg/m^2 on Day 1 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles.	Drug: Necitumumab Drug: Gemcitabine Drug: Cisplatin
Gemcitabine + Cisplatin	Active Comparator	Phase 2 Randomized: Gemcitabine at fixed dose determined in Phase 1b (1000 to 1250 mg/m^2) on Day 1 and Day 8 of every 21 day cycle,administered as an IV infusion over approximately 30 minutes for a maximum of 4 cycles. Cisplatin 75 mg/m^2 on Day 1 of every 21 day cycle, administered as an IV infusion over approximately 120 minutes for a maximum of 4 cycles .	Drug: Gemcitabine Drug: Cisplatin

Name	Type	Description	Arm Group Labels	Other Names
Necitumumab	Drug	Administered IV	Necitumumab + Gem and Cis	IMC-11F8

Measure	Description	Time Frame
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)	DLT was defined as any of the following events graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, when the event occurred within 21 days from Day 1 in Cycle 1 and was considered to be definitely or probably related to necitumumab and/or gemcitabine-cisplatin chemotherapy: Grade 4 neutropenia ≥ 7 days, Grade ≥ 3 febrile neutropenia except for transient febrile neutropenia (Grade 3 neutropenia with fever ≥ 38.5 degrees Celsius (°C) for ≤ 24 hours), Grade 3 thrombocytopenia requiring platelet substitution, Grade 4 thrombocytopenia, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, arthralgia, myalgia, asthenia, fatigue, diarrhea, constipation, anorexia), any toxicity leading to the omission of necitumumab on Day 8 or 15 (for participants for whom necitumumab was delayed from Days 8 to 15) during the Cycle 1.	Day 1 to Day 21 in Cycle 1 (Up To 21 days)
Phase 2: Overall Survival (OS)	OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive.	From Date of Randomization until Death Due to Any Cause (Up To 39 Months)

Measure	Description	Time Frame
Phase 2: Progression Free Survival (PFS)	PFS defined as time from date of randomization until first radiographic documentation of measured progressive disease(PD) defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis,the PFS time censored at last adequate tumor assessment date.The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy.

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Aichi		464-8681

PubMed Identifier	Type	Citation	Retractions
30797492	Derived	Watanabe S, Yoshioka H, Sakai H, Hotta K, Takenoyama M, Yamada K, Sugawara S, Takiguchi Y, Hosomi Y, Tomii K, Niho S, Yamamoto N, Nishio M, Ohe Y, Kato T, Takahashi T, Kamada A, Suzukawa K, Omori Y, Enatsu S, Nakagawa K, Tamura T. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan. Lung Cancer. 2019 Mar;129:55-62. doi: 10.1016/j.lungcan.2019.01.005. Epub 2019 Jan 16.

ID	Title	Description
FG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 (milligrams per square meter) was administered over approximately 30 minutes intravenously (IV) on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 12, 2016	Jun 5, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)

DLT was defined as any of the following events graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, when the event occurred within 21 days from Day 1 in Cycle 1 and was considered to be definitely or probably related to necitumumab and/or gemcitabine-cisplatin chemotherapy: Grade 4 neutropenia ≥ 7 days, Grade ≥ 3 febrile neutropenia except for transient febrile neutropenia (Grade 3 neutropenia with fever ≥ 38.5 degrees Celsius (°C) for ≤ 24 hours), Grade 3 thrombocytopenia requiring platelet substitution, Grade 4 thrombocytopenia, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, arthralgia, myalgia, asthenia, fatigue, diarrhea, constipation, anorexia), any toxicity leading to the omission of necitumumab on Day 8 or 15 (for participants for whom necitumumab was delayed from Days 8 to 15) during the Cycle 1.

All enrolled participants who received at least one dose of study drug during study Phase 1b.

Posted

Count of Participants

Participants

Day 1 to Day 21 in Cycle 1 (Up To 21 days)

ID	Title	Description
OG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 1b: Cohort 2	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Units	Counts
Participants	OG0003 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Primary

Phase 2: Overall Survival (OS)

OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive.

All randomized participants who received at least one dose of study drug during study Phase 2. Censored participants in the GC+N Arm = 27 and in the GC Arm = 17.

Posted

Median

95% Confidence Interval

Months

From Date of Randomization until Death Due to Any Cause (Up To 39 Months)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 2: GC (Gemcitabine, Cisplatin)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.

Secondary

Phase 2: Progression Free Survival (PFS)

PFS defined as time from date of randomization until first radiographic documentation of measured progressive disease(PD) defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis,the PFS time censored at last adequate tumor assessment date.The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy.

All randomized participants who received at least one dose of study during study Phase 2. Censored participants in the GC+N Arm = 6 and in the GC Arm = 10.

Posted

Median

95% Confidence Interval

Months

From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up To 39 Months)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Secondary

Phase 1b: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])

ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

All randomized participants who received at least one dose of study drug during study Phase 1b.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to Measured Progressive Disease (Up To 39 Months)

ID	Title	Description
OG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001

Secondary

Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])

All randomized participants who received at least one dose of study drug during study Phase 2.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to Measured Progressive Disease (Up To 39 Months)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001

Secondary

Phase 2: Time to Treatment Failure (TTF)

TTF was time from the date of randomization until the date of the first observation of radiographically documented progressive disease (PD), death due to any cause, discontinuation of treatment for any reason, or initiation of new anticancer therapy. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Time to treatment failure was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.

All randomized participants who received at least one dose of study drug during study Phase 2. Censored participants in the GC+N Arm = 1 and in the GC Arm = 0.

Posted

Median

95% Confidence Interval

Months

From Date of Randomization to Measured Progressive Disease, Death Due to Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up To 39 Months)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001

Secondary

Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Index Score

EQ-5D measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression. 3 severity levels: no, some, severe problems. The index score was calculated from a set of item weights to derive a score on a theoretical scale of 0 to 1, with 1 representing the best health status and zero representing death based on item weights for the Japanese population. One Cycle = 3 weeks and it can be delayed up to 6 weeks.

All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline EQ-5D data during study Phase 2.

Posted

Mean

Standard Deviation

Score on a scale

Baseline, Cycle 4 (Cycle = 3 weeks)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 2: GC (Gemcitabine, Cisplatin)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.

Secondary

Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Visual Analog Scale (VAS)

EQ-5D VAS allowed participants to rate their present health condition. Possible scores ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). One Cycle = 3 weeks and it can be delayed up to 6 weeks.

All randomized participants who received at least one dose of study drug and had had evaluable baseline and post-baseline EQ-5D data during study Phase 2.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Cycle 4 (Cycle = 3 weeks)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 2: GC (Gemcitabine, Cisplatin)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.

Secondary

Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS)

The LCSS is a validated and reliable instrument to assess lung cancer-specific symptoms and their impact on QOL.The LCSS total score was defined as the mean of the 9 items of the scale and the average symptom burden index (ASBI) is defined as the mean of 6 symptom-specific lung cancer questions. Each of the 9 symptom or summary items is assessed on a 100-mm visual analogue scale (VAS), with 0 representing no symptoms or better QOL.

All randomized participants who received at least one dose of study drug had evaluable baseline and post-baseline LCSS data. One Cycle = 3 weeks and it can be delayed up to 6 weeks.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Cycle 4 (Cycle = 3 weeks)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 2: GC (Gemcitabine, Cisplatin)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.

Secondary

Phase 1b: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

The Cmax is observed maximum serum concentration, taken directly from the serum concentration-time profile.

All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b. In cohort 1 (cycle 3), zero participants were analyzed because no data was collected for the outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

micrograms/milliliter (µg/ml)

Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion

ID	Title	Description
OG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 1b: Cohort 2	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Secondary

Phase 1b: PK: Cmax of Gemcitabine and Cisplatin

The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.

All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

Gemcitabine: Cycle 1(C1) Day1(D1): Predose, End-of-infusion and 0.5, 1, 2 h post-end-of-infusion; Cisplatin:C1 D1: Predose, End-of-infusion and 3, 21, 93, 165 h post-end-of-infusion

ID	Title	Description
OG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 1b: Cohort 2	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Secondary

Phase 1b: PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Necitumumab

The AUC(0-infinity) is area under the serum concentration-time curve from time zero to infinite time.

All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b. In cohort 1 and 2 (cycle 3), zero participants were analyzed because no data was collected for the outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

microgram*hour per milliliter (µg*h/mL)

Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion

ID	Title	Description
OG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 1b: Cohort 2	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Secondary

Phase 1b: PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Gemcitabine and Cisplatin

The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time.

All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 1b. In cohort 1 (cisplatin), zero participants were analyzed because no data was collected for the outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram*hour per milliliter (ng*h/mL)

Gemcitabine: C1D1: Predose, End-of-infusion and 0.5, 1, 2 h post-end-of-infusion; Cisplatin:C1D1: Predose, End-of-infusion and 3, 21, 93, 165 h post-end-of-infusion

ID	Title	Description
OG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
OG001	Phase 1b: Cohort 2	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Secondary

Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab

The minimum observed serum concentration (Ctrough) of Necitumumab was evaluated.

All enrolled participants who had adequate data to calculate at least 1 PK parameter during study Phase 2.

Posted

Geometric Mean

Geometric Coefficient of Variation

microgram per milliliter (µg/mL)

Predose Day 1 of Cycle 1, 2, 3, 4, and every 2 cycles after Cycle 5

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Units	Counts
Participants	OG000

Secondary

Phase 2: Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity)

A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point.

All enrolled participants who received at least 1 dose of drug and had evaluable data for antibodies during study Phase 2.

Posted

Count of Participants

Participants

Baseline up to 30 Days Post Last Infusion (estimated up to 39 months)

ID	Title	Description
OG000	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bone marrow toxicity	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG0031 events1 affected91 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0026 events6 affected90 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Diverticular perforation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Appendicitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Lung infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Pneumonia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0026 events6 affected90 at risk EG003
Retroperitoneal abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Septic shock	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Compression fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Tracheal haemorrhage	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Lymphangiosis carcinomatosa	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Cerebral ischaemia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Optic neuritis	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Presyncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Spinal cord paralysis	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Delirium	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Panic disorder	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pulmonary artery thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Shock	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Superior vena cava syndrome	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0018 events5 affected6 at risk EG00255 events43 affected90 at risk EG00365 events53 affected91 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0026 events6 affected90 at risk EG003
Haemorrhagic diathesis	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0003 events1 affected3 at risk EG00110 events4 affected6 at risk EG00210 events5 affected90 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0003 events1 affected3 at risk EG0018 events3 affected6 at risk EG00219 events13 affected90 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0004 events2 affected3 at risk EG0014 events4 affected6 at risk EG0022 events2 affected90 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0021 events1 affected90 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0021 events1 affected90 at risk EG003
Atrial tachycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Atrioventricular block second degree	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Bundle branch block left	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Conduction disorder	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Palpitations	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Cataract	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Chalazion	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Dry eye	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Eye discharge	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Eye disorder	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Optic nerve disorder	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Trichiasis	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0027 events5 affected90 at risk EG003
Anal erosion	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Anal fistula	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0026 events6 affected90 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected3 at risk EG0015 events4 affected6 at risk EG00276 events58 affected90 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0012 events2 affected6 at risk EG00243 events26 affected90 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0007 events2 affected3 at risk EG00110 events5 affected6 at risk EG002111 events55 affected90 at risk EG003
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Periodontal disease	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected3 at risk EG0015 events3 affected6 at risk EG00248 events37 affected90 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0015 events3 affected6 at risk EG00228 events17 affected90 at risk EG003
Asthenia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events2 affected90 at risk EG003
Chest discomfort	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Chest pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Chills	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Extravasation	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Face oedema	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0027 events4 affected90 at risk EG003
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0014 events3 affected6 at risk EG00239 events17 affected90 at risk EG003
Hypothermia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Influenza like illness	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Infusion site extravasation	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0024 events4 affected90 at risk EG003
Infusion site reaction	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Injection site pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events1 affected90 at risk EG003
Injection site reaction	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0027 events4 affected90 at risk EG003
Localised oedema	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Malaise	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0012 events2 affected6 at risk EG00249 events34 affected90 at risk EG003
Mucosal inflammation	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0025 events3 affected90 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Oedema	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0021 events1 affected90 at risk EG003
Oedema peripheral	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG00216 events10 affected90 at risk EG003
Pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG00218 events18 affected90 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Angular cheilitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Bronchitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0023 events2 affected90 at risk EG003
Candida infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0012 events1 affected6 at risk EG0029 events7 affected90 at risk EG003
Dacryocanaliculitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Dermatophytosis of nail	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Enteritis infectious	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Eye infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Folliculitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Hordeolum	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Influenza	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Lip infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Lung infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0028 events8 affected90 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0024 events2 affected90 at risk EG003
Onychomycosis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Oral herpes	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Paronychia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0013 events2 affected6 at risk EG00248 events44 affected90 at risk EG003
Periodontitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0021 events1 affected90 at risk EG003
Pleural infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pneumonia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0022 events2 affected90 at risk EG003
Rash pustular	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Skin infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Tinea infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Tinea manuum	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Tinea pedis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG00212 events11 affected90 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0025 events5 affected90 at risk EG003
Wound infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Compression fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Injury	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Injury corneal	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Radiation oesophagitis	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Tracheal haemorrhage	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Venous injury	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Wound complication	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected3 at risk EG0014 events1 affected6 at risk EG00228 events18 affected90 at risk EG003
Amylase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events1 affected90 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events1 affected6 at risk EG00227 events17 affected90 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events1 affected6 at risk EG00210 events9 affected90 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0025 events3 affected90 at risk EG003
Blood creatine phosphokinase decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0025 events5 affected90 at risk EG003
Blood creatinine increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG00212 events8 affected90 at risk EG003
Blood urea increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events2 affected90 at risk EG003
C-reactive protein increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Creatinine renal clearance decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Electrocardiogram qt prolonged	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Electrocardiogram st segment depression	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Electrocardiogram t wave inversion	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0028 events7 affected90 at risk EG003
Glucose urine present	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG00211 events4 affected90 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected3 at risk EG0017 events3 affected6 at risk EG002119 events53 affected90 at risk EG003
Platelet count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0015 events2 affected6 at risk EG00296 events49 affected90 at risk EG003
Platelet count increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events1 affected90 at risk EG003
Protein total decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Urine output decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Weight decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG00216 events13 affected90 at risk EG003
Weight increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG00212 events7 affected90 at risk EG003
White blood cell count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected3 at risk EG0012 events2 affected6 at risk EG00299 events49 affected90 at risk EG003
White blood cells urine positive	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0006 events2 affected3 at risk EG0019 events4 affected6 at risk EG002112 events62 affected90 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0025 events4 affected90 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events2 affected90 at risk EG003
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0024 events3 affected90 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0029 events6 affected90 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG00223 events8 affected90 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events2 affected90 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected6 at risk EG00214 events12 affected90 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0015 events1 affected6 at risk EG00215 events9 affected90 at risk EG003
Hypochloraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0024 events3 affected90 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0025 events3 affected90 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0017 events2 affected6 at risk EG00254 events35 affected90 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0014 events2 affected6 at risk EG00215 events12 affected90 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0024 events4 affected90 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events2 affected6 at risk EG0025 events5 affected90 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0025 events4 affected90 at risk EG003
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events1 affected90 at risk EG003
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Lymphangiosis carcinomatosa	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0026 events6 affected90 at risk EG003
Coordination abnormal	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Dementia with lewy bodies	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Depressed level of consciousness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected6 at risk EG0025 events5 affected90 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected3 at risk EG0012 events2 affected6 at risk EG00222 events19 affected90 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0027 events7 affected90 at risk EG003
Paralysis	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Paralysis recurrent laryngeal nerve	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0024 events4 affected90 at risk EG003
Presyncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Tremor	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Vagus nerve disorder	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Adjustment disorder	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Delirium	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Depression	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected3 at risk EG0011 events1 affected6 at risk EG00217 events15 affected90 at risk EG003
Panic disorder	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events1 affected90 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0025 events5 affected90 at risk EG003
Haemoglobinuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0028 events7 affected90 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected5 at risk EG0020 events0 affected79 at risk EG003
Scrotal swelling	Reproductive system and breast disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected5 at risk EG0021 events1 affected79 at risk EG003
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Bronchostenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Dysaesthesia pharynx	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events3 affected6 at risk EG00212 events12 affected90 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0024 events4 affected90 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 events2 affected3 at risk EG0015 events2 affected6 at risk EG00268 events42 affected90 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Laryngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Nasal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Organising pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0020 events0 affected90 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events1 affected90 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events3 affected6 at risk EG00218 events18 affected90 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events2 affected90 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected3 at risk EG0013 events3 affected6 at risk EG00279 events72 affected90 at risk EG003
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0013 events3 affected6 at risk EG00249 events48 affected90 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Miliaria	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Palmar erythema	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0026 events6 affected90 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0029 events8 affected90 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected6 at risk EG00211 events10 affected90 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected6 at risk EG0028 events6 affected90 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0025 events5 affected90 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Skin toxicity	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0024 events4 affected90 at risk EG003
Dermabrasion	Surgical and medical procedures	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Arteriosclerosis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Embolism	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0024 events4 affected90 at risk EG003
Hot flush	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Hypertension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0025 events5 affected90 at risk EG003
Hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0022 events2 affected90 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected90 at risk EG003
Phlebitis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events3 affected90 at risk EG003
Thrombophlebitis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Thrombosis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected90 at risk EG003
Vascular pain	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0015 events2 affected6 at risk EG0027 events3 affected90 at risk EG003
Vasculitis	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0026 events4 affected90 at risk EG003

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds

ID	Title	Description
BG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
BG001	Phase 1b: Cohort 2	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
BG002	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.
BG003	Phase 2: GC (Gemcitabine, Cisplatin)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1b: Cohort 1	Gemcitabine at a dose of 1000 mg/m^2 (milligrams per square meter) was administered over approximately 30 minutes intravenously (IV) on Days 1 and 8 of each cycle for a maximum of 4 cycles.	0	3	1	3	3	3
EG001	Phase 1b: Cohort 2	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles.	0	6	0	6	6	6
EG002	Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles. Necitumumab at a dose of 800 mg was administered over approximately 50 minutes intravenously IV on Days 1 and 8 of each 3-week cycle.	63	90	32	90	90	90
EG003	Phase 2: GC (Gemcitabine, Cisplatin)	Gemcitabine at a dose of 1250 mg/m^2 was administered over approximately 30 minutes IV on Days 1 and 8 of each cycle for a maximum of 4 cycles. Cisplatin at a dose of 75 mg/m^2 was administered over approximately 120 minutes IV on Day 1 for a maximum of 4 cycles.	74	91	22	91	91	91