Study of Ibrutinib vs Placebo, in Combination With Nab-pa... | NCT02436668

Label	Type	Description	Intervention Names
Ibrutinib	Active Comparator	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine	Drug: Ibrutinib Drug: Gemcitabine Drug: Nab-paclitaxel
Placebo	Placebo Comparator	Placebo daily in combination with: Nab-paclitaxel and gemcitabine	Drug: Gemcitabine Drug: Nab-paclitaxel

Name	Type	Description	Arm Group Labels	Other Names
Ibrutinib	Drug		Ibrutinib	IMBRUVICA®
Gemcitabine

Measure	Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization until disease progression per RECIST 1.1 criteria assessed by investigator, or death from any cause, whichever occurs first.	Results at an overall median follow-up of 24.87 months
Overall Survival (OS)	OS, is defined as the time from date of randomization until date of death from any cause.	Results at an overall median follow-up of 24.87 months

Measure	Description	Time Frame
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine.	This is a measure of percentage of subjects with Treatment Emergent Adverse Events Grade 3 or above collected Up to 30 days after the last participating subject discontinues study drug.	Results at an overall median follow-up of 24.87 months

Name	Affiliation	Role
George Cole, MD	Pharmacyclics LLC.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Oncology Specialties, PC; Clearview Cancer Institute		Huntsville	Alabama	35805	United States
Arizona Center for Cancer Care

ID	Title	Description
FG000	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
FG001	Ibrutinib+Gemcitabine+Nab-paclitaxel

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jan 15, 2018	Oct 31, 2019

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

Progression Free Survival (PFS)

PFS is defined as the time from the date of randomization until disease progression per RECIST 1.1 criteria assessed by investigator, or death from any cause, whichever occurs first.

Posted

Median

95% Confidence Interval

Months

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.
OG001	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion

Units	Counts
Participants	OG000211 OG001213

Title

Denominators

Categories

Title	Measurements
	OG0005.32(3.75 to 5.49) OG0016.01(5.45 to 7.16)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The treatment effect was tested with an stratified log rank test. Hazard ratio is estimated using Cox regression model stratified by the three randomization stratification factors [KPS (70 80 vs. 90-100), liver metastasis (present vs. absent), and age (≤65 vs. >65)] and with treatment as the only covariate.	Log Rank		<0.0001	P-value is from log-rank test stratified by the three randomization stratification factors [KPS (70-80 vs. 90-100), liver metastasis (present vs. absent), and age (≤65 vs. >65)].	Hazard Ratio (HR)	1.525			2-Sided	95	1.241	1.873					Superiority

Primary

Overall Survival (OS)

OS, is defined as the time from date of randomization until date of death from any cause.

Posted

Median

95% Confidence Interval

Months

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.
OG001	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine.

This is a measure of percentage of subjects with Treatment Emergent Adverse Events Grade 3 or above collected Up to 30 days after the last participating subject discontinues study drug.

The safety population included 420 subjects and was used for the analyses of all safety endpoints and included all subjects in the ITT population who received at least 1 dose of study drug (ibrutinib, placebo, nab-paclitaxel, or gemcitabine). The data sets analyzed are summarized in the following table.

Posted

Number

percentage of participants

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
OG001	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.

Secondary

Overall Response Rate

ORR is defined as the percentage of subjects who achieve a complete response or partial response, based on investigator assessment according to RECIST 1.1.

Posted

Number

95% Confidence Interval

percentage of Patients

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
OG001	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.

Units	Counts
Participants	OG000

Secondary

Clinical Benefit Response

Subject achieved a ≥50% reduction in pain intensity (Memorial Pain Assessment Card [MPAC]) or analgesic consumption, or a 20-point or greater improvement in KPS for a period of at least 4 consecutive weeks, without showing any sustained worsening in other parameters.

OR Subject was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain (≥7% increase maintained for ≥4 weeks) not due to fluid accumulation (Burris 1997).

Clinical benefit response rate was not analyzed due to incomplete data for the analgesic use. Data for subjects who "Achieved a >=50% reduction in pain intensity", "20-point or greater improvement in KPS (>=4 consecutive weeks)", "Sustained weight gain (>=7% increase maintained for >=4 weeks) not due to fluid accumulation"are reported.

Posted

Number

percentage of patients

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
OG001	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion. I

Secondary

Carbohydrate Antigen 19-9 (CA19-9) Response

The CA19-9 response rate is defined as the percentage of subjects with a decline of 20%, 90%, and other thresholds considered clinically meaningful, from baseline. This is a percentage of patients with > or = 60% reduction from baseline.

Posted

Number

95% Confidence Interval

percentage of patients

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
OG001	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.

Units	Counts
Participants

Secondary

Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).

Unit is the month: TUDD1 - the time between random & 1st occurrence of a decrease in QLQ-C30 score ≥10 pts w/o improvement in QoL score of ≥10 points or any further QoL data due to deterioration. The proportion of subjects who met the "responder" criteria prior to subsequent anticancer therapy initiation. Response defined as achievement of a ≥50% reduction in MPAC visual analog scale which measures pain intensity or analgesic consumption, or a ≥20-point improvement from baseline in KPS sustained for a period of ≥ 4 consecutive weeks without showing any sustained worsening from baseline in any of the other parameters OR Subject stable on all parameters (pain and KPS), & showed a marked, sustained weight gain (≥7% increase from baseline maintained for ≥4 weeks) not due to fluid accumulation.

Posted

Median

95% Confidence Interval

months

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
OG001	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.

Secondary

Rate of Venous Thromboembolic Events (VTE)

The VTE rate is defined as percentage of subjects with Venous thromboembolic events (SMQ) per investigator assessment.

Posted

Number

95% Confidence Interval

Percentage of Participants

Results at an overall median follow-up of 24.87 months

ID	Title	Description
OG000	Placebo+Gemcitabine+Nab-Paclitaxel	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
OG001	Ibrutinib+Gemcitabine+Nab-paclitaxel	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib was administered orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG00013 events9 affected212 at risk EG0017 events7 affected208 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0017 events6 affected208 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG0006 events4 affected212 at risk EG0018 events4 affected208 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0011 events1 affected208 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Haemorrhagic diathesis	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Atrial fibrillation	Cardiac disorders	MedDRA Version 21.0	Systematic Assessment	EG0004 events4 affected212 at risk EG0014 events3 affected208 at risk
Left ventricular failure	Cardiac disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Cardiac failure	Cardiac disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0010 events0 affected208 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Sinus tachycardia	Cardiac disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Cataract	Eye disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00010 events9 affected212 at risk EG00117 events14 affected208 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0006 events6 affected212 at risk EG0019 events5 affected208 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00012 events11 affected212 at risk EG0017 events4 affected208 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events1 affected212 at risk EG0016 events4 affected208 at risk
Duodenal obstruction	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0013 events3 affected208 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0014 events3 affected208 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0007 events7 affected212 at risk EG0016 events3 affected208 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0012 events2 affected208 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0012 events2 affected208 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events2 affected208 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0011 events1 affected208 at risk
Duodenal stenosis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Flatulence	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Inguinal hernia strangulated	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Intussusception	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Melaena	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Neutropenic colitis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Pneumoperitoneum	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Small intestinal ulcer haemorrhage	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Ascites	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0010 events0 affected208 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Haematemesis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Obstruction gastric	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0010 events0 affected208 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0010 events0 affected208 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events1 affected212 at risk EG0010 events0 affected208 at risk
Retching	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Pyrexia	General disorders	MedDRA Version 21.0	Systematic Assessment	EG00020 events17 affected212 at risk EG00116 events13 affected208 at risk
Asthenia	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0007 events7 affected212 at risk EG0018 events6 affected208 at risk
General physical health deterioration	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0006 events5 affected212 at risk EG0015 events4 affected208 at risk
Mucosal inflammation	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events2 affected208 at risk
Fatigue	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Chest pain	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Chills	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Gait disturbance	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Generalised oedema	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Hyperthermia	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Pain	General disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Cholangitis	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0006 events4 affected212 at risk EG00114 events9 affected208 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events2 affected208 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0011 events1 affected208 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0011 events1 affected208 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events1 affected208 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Jaundice	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0011 events1 affected208 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0004 events4 affected212 at risk EG0010 events0 affected208 at risk
Biliary dilatation	Hepatobiliary disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Pneumonia	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG00011 events8 affected212 at risk EG00114 events13 affected208 at risk
Cellulitis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0014 events4 affected208 at risk
Infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0014 events4 affected208 at risk
Liver abscess	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0014 events4 affected208 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0014 events4 affected208 at risk
Bacteraemia	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0013 events3 affected208 at risk
Escherichia sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0002 events1 affected212 at risk EG0013 events3 affected208 at risk
Biliary tract infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0012 events2 affected208 at risk
Gastroenteritis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0012 events2 affected208 at risk
Neutropenic sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0012 events2 affected208 at risk
Respiratory tract infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events2 affected208 at risk
Abdominal sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Biliary sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0011 events1 affected208 at risk
Candida sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events1 affected208 at risk
Clostridium difficile infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Cystitis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Empyema	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Enterobacter bacteraemia	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Gastrointestinal infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Infectious colitis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0004 events4 affected212 at risk EG0011 events1 affected208 at risk
Pneumonia bacterial	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Pulmonary sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events1 affected208 at risk
Pyelonephritis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Pyelonephritis acute	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Septic shock	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0004 events3 affected212 at risk EG0012 events1 affected208 at risk
Vascular device infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Anal abscess	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Bronchitis bacterial	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Device related infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0005 events4 affected212 at risk EG0010 events0 affected208 at risk
Diverticulitis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Erysipelas	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Intervertebral discitis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Peritonitis bacterial	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0005 events4 affected212 at risk EG0010 events0 affected208 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG0002 events1 affected212 at risk EG0010 events0 affected208 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events1 affected208 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Bone contusion	Injury, poisoning and procedural complications	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Alanine aminotransferase increased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Blood bilirubin increased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG0004 events2 affected212 at risk EG0012 events1 affected208 at risk
Blood creatinine increased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Aspartate aminotransferase increased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Neutrophil count decreased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Platelet count decreased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Transaminases increased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG0003 events2 affected212 at risk EG0010 events0 affected208 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0005 events5 affected212 at risk EG0011 events1 affected208 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events1 affected208 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Enzyme abnormality	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0016 events4 affected208 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0010 events0 affected208 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 21.0	Systematic Assessment	EG0008 events6 affected212 at risk EG0017 events6 affected208 at risk
Pancreatic carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 21.0	Systematic Assessment	EG0008 events5 affected212 at risk EG0016 events5 affected208 at risk
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 21.0	Systematic Assessment	EG0004 events3 affected212 at risk EG0013 events2 affected208 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 21.0	Systematic Assessment	EG0004 events4 affected212 at risk EG0012 events2 affected208 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Depression	Psychiatric disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Suicide attempt	Psychiatric disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Renal failure	Renal and urinary disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0014 events3 affected208 at risk
Urinary retention	Renal and urinary disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0011 events1 affected208 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA Version 21.0	Systematic Assessment	EG0005 events4 affected212 at risk EG0010 events0 affected208 at risk
Azotaemia	Renal and urinary disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events3 affected212 at risk EG0014 events3 affected208 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0012 events2 affected208 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0011 events1 affected208 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0011 events1 affected208 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0003 events2 affected212 at risk EG0010 events0 affected208 at risk
Hypotension	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0012 events2 affected208 at risk
Embolism	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Peripheral ischaemia	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Arterial haemorrhage	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Deep vein thrombosis	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Venous thrombosis	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Venous thrombosis limb	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Syncope	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0002 events2 affected212 at risk EG0013 events3 affected208 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Guillain-Barre syndrome	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0011 events1 affected208 at risk
Hydrocephalus	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Ischaemic cerebral infarction	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Ischaemic stroke	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Peripheral sensorimotor neuropathy	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Seizure	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Wernicke's encephalopathy	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0000 events0 affected212 at risk EG0011 events1 affected208 at risk
Cerebral infarction	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Epilepsy	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk
Confusional state	Psychiatric disorders	MedDRA Version 21.0	Systematic Assessment	EG0001 events1 affected212 at risk EG0010 events0 affected208 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG000309 events95 affected212 at risk EG001289 events90 affected208 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG000208 events55 affected212 at risk EG001221 events75 affected208 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG000328 events84 affected212 at risk EG001139 events68 affected208 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA Version 21.0	Systematic Assessment	EG00061 events18 affected212 at risk EG00119 events15 affected208 at risk
Vision blurred	Eye disorders	MedDRA Version 21.0	Systematic Assessment	EG00018 events15 affected212 at risk EG00120 events17 affected208 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG000240 events109 affected212 at risk EG001357 events147 affected208 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG000242 events107 affected212 at risk EG001228 events116 affected208 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG000184 events86 affected212 at risk EG001169 events85 affected208 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00096 events78 affected212 at risk EG00191 events68 affected208 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00099 events67 affected212 at risk EG00194 events63 affected208 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00040 events27 affected212 at risk EG00164 events38 affected208 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00028 events21 affected212 at risk EG00150 events36 affected208 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00026 events21 affected212 at risk EG00138 events34 affected208 at risk
Ascites	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00035 events25 affected212 at risk EG00130 events21 affected208 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00013 events13 affected212 at risk EG00115 events13 affected208 at risk
Asthenia	General disorders	MedDRA Version 21.0	Systematic Assessment	EG000283 events93 affected212 at risk EG001311 events100 affected208 at risk
Pyrexia	General disorders	MedDRA Version 21.0	Systematic Assessment	EG000181 events82 affected212 at risk EG001150 events85 affected208 at risk
Fatigue	General disorders	MedDRA Version 21.0	Systematic Assessment	EG000170 events65 affected212 at risk EG001149 events78 affected208 at risk
Oedema peripheral	General disorders	MedDRA Version 21.0	Systematic Assessment	EG000143 events77 affected212 at risk EG00197 events60 affected208 at risk
Mucosal inflammation	General disorders	MedDRA Version 21.0	Systematic Assessment	EG00029 events19 affected212 at risk EG00136 events24 affected208 at risk
Chills	General disorders	MedDRA Version 21.0	Systematic Assessment	EG00021 events15 affected212 at risk EG00124 events21 affected208 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG00025 events16 affected212 at risk EG00123 events16 affected208 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 21.0	Systematic Assessment	EG00017 events15 affected212 at risk EG00110 events7 affected208 at risk
Weight decreased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG00033 events21 affected212 at risk EG00119 events14 affected208 at risk
Platelet count decreased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG00061 events17 affected212 at risk EG00126 events13 affected208 at risk
Alanine aminotransferase increased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG00042 events25 affected212 at risk EG00116 events12 affected208 at risk
Neutrophil count decreased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG00048 events19 affected212 at risk EG00119 events11 affected208 at risk
Aspartate aminotransferase increased	Investigations	MedDRA Version 21.0	Systematic Assessment	EG00034 events18 affected212 at risk EG00112 events8 affected208 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG000129 events76 affected212 at risk EG001135 events85 affected208 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG00032 events20 affected212 at risk EG00137 events25 affected208 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG00028 events16 affected212 at risk EG00124 events17 affected208 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG00016 events7 affected212 at risk EG00114 events11 affected208 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 21.0	Systematic Assessment	EG00014 events12 affected212 at risk EG0015 events5 affected208 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00058 events35 affected212 at risk EG00136 events28 affected208 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00038 events25 affected212 at risk EG00131 events25 affected208 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00030 events26 affected212 at risk EG00120 events17 affected208 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00031 events24 affected212 at risk EG00124 events17 affected208 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00013 events11 affected212 at risk EG00113 events11 affected208 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00015 events11 affected212 at risk EG0015 events5 affected208 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG000153 events63 affected212 at risk EG001171 events69 affected208 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG00042 events20 affected212 at risk EG00179 events27 affected208 at risk
Headache	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG00024 events20 affected212 at risk EG00125 events21 affected208 at risk
Dizziness	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG00022 events20 affected212 at risk EG00122 events20 affected208 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG00033 events26 affected212 at risk EG00124 events19 affected208 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG00028 events14 affected212 at risk EG00133 events15 affected208 at risk
Neurotoxicity	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG00047 events18 affected212 at risk EG00140 events14 affected208 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA Version 21.0	Systematic Assessment	EG00023 events11 affected212 at risk EG00130 events13 affected208 at risk
Insomnia	Psychiatric disorders	MedDRA Version 21.0	Systematic Assessment	EG00036 events34 affected212 at risk EG00123 events20 affected208 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00027 events21 affected212 at risk EG00141 events36 affected208 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00064 events43 affected212 at risk EG00134 events25 affected208 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00047 events42 affected212 at risk EG00119 events15 affected208 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00022 events16 affected212 at risk EG00114 events9 affected208 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Systematic Assessment	EG00016 events12 affected212 at risk EG0017 events7 affected208 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG000119 events87 affected212 at risk EG001130 events90 affected208 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00042 events28 affected212 at risk EG00128 events23 affected208 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG0007 events6 affected212 at risk EG00116 events14 affected208 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00021 events15 affected212 at risk EG00116 events12 affected208 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Systematic Assessment	EG00036 events25 affected212 at risk EG0018 events8 affected208 at risk
Hypotension	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG00015 events13 affected212 at risk EG00115 events12 affected208 at risk
Hypertension	Vascular disorders	MedDRA Version 21.0	Systematic Assessment	EG00034 events13 affected212 at risk EG00133 events11 affected208 at risk

ID	Title	Description
BG000	Pbo+n-P/G	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion.
BG001	Ibr+n-P/G	Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib- orally once daily at a starting dose of 560 mg. Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion
BG002	Total	Total of all reporting groups

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo (Plus Nab-paclitaxel and Gemcitabine)	Placebo daily in combination with: Nab-paclitaxel and gemcitabine Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion	188	212	127	212	211	212
EG001	Ibrutinib (Plus Nab-paclitaxel and Gemcitabine)	Ibrutinib 560 mg (4 x 140 mg capsules) (or placebo) was administered orally once daily beginning on Day 1 of Cycle 1 of the treatment phase, with the first dose of ibrutinib given no more than 72 hours after randomization Nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 were administered on Days 1, 8, and 15 of each 28-day cycle, each as a 30- to 40-minute intravenous infusion	189	208	112	208	208	208

ID	Term
C551803	ibrutinib
D000093542	Gemcitabine
C520255	130-nm albumin-bound paclitaxel