Trial Outcomes & Findings for QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas (NCT NCT01231347)

NCT ID: NCT01231347

Last Updated: 2024-07-16

Results Overview

The primary endpoint of the study was OS, defined as the time from randomization to death.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

800 participants

Primary outcome timeframe

From randomization up to 20 months

Results posted on

2024-07-16

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo + Gemcitabine Arm 1: AMG 479-placebo IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle Placebo: Placebo administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 12 mg/kg Dose + Gemcitabine Arm 2: AMG 479 12 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 20 mg/kg + Gemcitabine Arm 3: AMG 479 20 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 20mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle
Overall Study STARTED	322	318	160
Overall Study COMPLETED	90	78	43
Overall Study NOT COMPLETED	232	240	117

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Gemcitabine Arm 1: AMG 479-placebo IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle Placebo: Placebo administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 12 mg/kg Dose + Gemcitabine Arm 2: AMG 479 12 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 20 mg/kg + Gemcitabine Arm 3: AMG 479 20 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 20mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle
Overall Study Full Consent withdrawn	19	19	11
Overall Study Lost to Follow-up	4	2	2
Overall Study Death	202	210	101
Overall Study other event	7	9	3

Baseline Characteristics

QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Gemcitabine n=322 Participants Arm 1: AMG 479-placebo IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle Placebo: Placebo administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 12 mg/kg Dose + Gemcitabine n=318 Participants Arm 2: AMG 479 12 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 20 mg/kg + Gemcitabine n=160 Participants Arm 3: AMG 479 20 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 20mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	Total n=800 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 9.6 • n=5 Participants	62.1 years STANDARD_DEVIATION 9.7 • n=7 Participants	62.7 years STANDARD_DEVIATION 10.1 • n=5 Participants	62.3 years STANDARD_DEVIATION 9.7 • n=4 Participants
Sex: Female, Male Female	134 Participants n=5 Participants	159 Participants n=7 Participants	75 Participants n=5 Participants	368 Participants n=4 Participants
Sex: Female, Male Male	188 Participants n=5 Participants	159 Participants n=7 Participants	85 Participants n=5 Participants	432 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	34 Participants n=5 Participants	19 Participants n=7 Participants	14 Participants n=5 Participants	67 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) White	253 Participants n=5 Participants	258 Participants n=7 Participants	129 Participants n=5 Participants	640 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	32 Participants n=5 Participants	37 Participants n=7 Participants	17 Participants n=5 Participants	86 Participants n=4 Participants
Region of Enrollment Europe	216 Participants n=5 Participants	219 Participants n=7 Participants	112 Participants n=5 Participants	547 Participants n=4 Participants
Region of Enrollment United States	26 Participants n=5 Participants	31 Participants n=7 Participants	13 Participants n=5 Participants	70 Participants n=4 Participants
Region of Enrollment Canada	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment Australia	13 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment Japan	30 Participants n=5 Participants	34 Participants n=7 Participants	16 Participants n=5 Participants	80 Participants n=4 Participants
Region of Enrollment North Asia	28 Participants n=5 Participants	16 Participants n=7 Participants	13 Participants n=5 Participants	57 Participants n=4 Participants
Region of Enrollment South America	5 Participants n=5 Participants	8 Participants n=7 Participants	1 Participants n=5 Participants	14 Participants n=4 Participants
Metastatic adenocarcinoma of the pancreas	322 Participants n=5 Participants	318 Participants n=7 Participants	160 Participants n=5 Participants	800 Participants n=4 Participants

PRIMARY outcome

Timeframe: From randomization up to 20 months

Population: Full analysis set =all randomized subjects

The primary endpoint of the study was OS, defined as the time from randomization to death.

Outcome measures

Outcome measures
Measure	AMG 479 12 mg/kg Dose + Gemcitabine n=318 Participants Arm 2: AMG 479 12 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 20 mg/kg + Gemcitabine n=160 Participants Arm 3: AMG 479 20 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 20mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	Placebo + Gemcitabine n=322 Participants Arm 1: AMG 479-placebo IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle Placebo: Placebo administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle
Determine if the Treatment of AMG 479 at 12 mg/kg and/or 20 mg/kg in Combination With Gemcitabine Improves Overall Survival as Compared With Placebo in Combination With Gemcitabine in Subjects With Metastatic Adenocarcinoma of the Pancreas	7.0 months Interval 6.2 to 8.5	7.1 months Interval 6.4 to 8.5	7.2 months Interval 6.3 to 8.2

Adverse Events

Placebo + Gemcitabine

Serious events: 33 serious events

Other events: 312 other events

Deaths: 202 deaths

AMG 479 12 mg/kg Dose + Gemcitabine

Serious events: 30 serious events

Other events: 308 other events

Deaths: 210 deaths

AMG 479 20 mg/kg + Gemcitabine

Serious events: 18 serious events

Other events: 159 other events

Deaths: 101 deaths

Serious adverse events

Other adverse events

Additional Information

Sandeep Bobby Reddy, Chief Medical Officer

ImmunityBio

Phone: 855-797-9277

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Placebo + Gemcitabine n=317 participants at risk Arm 1: AMG 479-placebo IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle Placebo: Placebo administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 12 mg/kg Dose + Gemcitabine n=315 participants at risk Arm 2: AMG 479 12 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 20 mg/kg + Gemcitabine n=160 participants at risk Arm 3: AMG 479 20 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 20mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle
Blood and lymphatic system disorders Anaemia	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Blood and lymphatic system disorders Thrombotic Thrombocytopenic Purpura	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Cardiac disorders Acute Myocardial Infarction	0.63% 2/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Cardiac disorders Cardiac Arrest	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Cardiac disorders Cardiac Failure	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.63% 2/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Cardiac disorders Cardiogenic Shock	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Abdominal Pain	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.63% 2/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Ascites	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Gastric Haemorrhage	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Ileus Paralytic	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Subileus	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders Death	1.6% 5/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders General Physical Health Deterioration	0.95% 3/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders Performance Status Decreased	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders Sudden Death	0.63% 2/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Hepatobiliary disorders Cholestasis	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Hepatobiliary disorders Jaundice	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Infections and infestations Peritonitis	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Infections and infestations Pneumonia	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Infections and infestations Respiratory Tract Infection	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Metabolism and nutrition disorders Cachexia	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	1.3% 4/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma Pancreas	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	1.2% 2/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases To Liver	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Carcinoma	1.6% 5/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	2.2% 7/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Carcinoma Metastatic	1.6% 5/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.95% 3/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	2.5% 4/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Neoplasm	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Haemorrhage	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Nervous system disorders Cerebrovascular Accident	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Nervous system disorders Coma Hepatic	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Renal and urinary disorders Renal Failure Acute	0.32% 1/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.32% 1/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	1.3% 4/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	1.9% 3/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Vascular disorders Hypotension	0.00% 0/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.00% 0/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	0.62% 1/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).

Other adverse events
Measure	Placebo + Gemcitabine n=317 participants at risk Arm 1: AMG 479-placebo IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle Placebo: Placebo administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 12 mg/kg Dose + Gemcitabine n=315 participants at risk Arm 2: AMG 479 12 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle	AMG 479 20 mg/kg + Gemcitabine n=160 participants at risk Arm 3: AMG 479 20 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle AMG 479: AMG 479 20mg/kg administered intravenously on days 1 and 15 of a 28 day cycle gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle
Gastrointestinal disorders Nausea	40.4% 128/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	42.2% 133/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	44.4% 71/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Blood and lymphatic system disorders Neutropenia	34.4% 109/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	37.1% 117/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	32.5% 52/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Blood and lymphatic system disorders Thrombocytopenia	29.7% 94/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	40.0% 126/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	33.8% 54/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders Fatigue	29.3% 93/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	35.2% 111/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	38.8% 62/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Metabolism and nutrition disorders Decreased Appetite	26.8% 85/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	29.8% 94/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	23.1% 37/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Vomiting	22.7% 72/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	28.3% 89/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	28.7% 46/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders Pyrexia	21.8% 69/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	21.3% 67/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	26.9% 43/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Blood and lymphatic system disorders Anaemia	24.0% 76/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	20.3% 64/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	22.5% 36/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Constipation	19.6% 62/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	26.0% 82/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	18.1% 29/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Diarrhoea	18.3% 58/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	26.7% 84/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	16.9% 27/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Gastrointestinal disorders Abdominal Pain	18.6% 59/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	21.9% 69/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	16.9% 27/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Metabolism and nutrition disorders Hyperglycaemia	9.8% 31/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	20.0% 63/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	26.2% 42/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Nervous system disorders Oedema Peripheral	18.3% 58/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	15.6% 49/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	15.6% 25/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Investigations Alanine Aminotransferase Increased	14.2% 45/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	19.4% 61/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	15.0% 24/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Investigations Aspartate Aminotransferase Increased	12.6% 40/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	17.8% 56/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	13.1% 21/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders Asthenia	14.2% 45/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	14.9% 47/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	11.2% 18/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Skin and subcutaneous tissue disorders Rash	10.7% 34/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	14.0% 44/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	15.0% 24/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Blood and lymphatic system disorders Leukopenia	10.1% 32/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	14.9% 47/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	9.4% 15/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Investigations Weight Decreased	9.1% 29/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	8.6% 27/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	14.4% 23/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Investigations Haemoglobin Decreased	6.9% 22/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	12.1% 38/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	5.6% 9/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Investigations Platelet Count Decreased	5.4% 17/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	9.8% 31/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	13.1% 21/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
General disorders Abdominal Pain Upper	5.4% 17/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	9.8% 31/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	13.1% 21/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Musculoskeletal and connective tissue disorders Back Pain	8.2% 26/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	7.0% 22/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	9.4% 15/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Investigations Blood Alkaline Phosphatase Increased	6.0% 19/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	9.8% 31/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	6.2% 10/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.6% 21/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	7.0% 22/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	7.5% 12/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Psychiatric disorders Insomnia	7.9% 25/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	6.3% 20/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	6.2% 10/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Respiratory, thoracic and mediastinal disorders Dysgeusia	4.1% 13/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	7.3% 23/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	8.1% 13/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).
Blood and lymphatic system disorders Hyperbilirubinaemia	3.5% 11/317 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	7.6% 24/315 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).	8.1% 13/160 • Adverse events were collected from screening through 30 days after the last dose of last protocol specified therapy, up to 20 months Mortality was assessed for all randomized participants (the Full Analysis Population). Adverse Events were assessed only in participants that received at least one dose of the study drug (the Safety Population).