Trial Outcomes & Findings for Study Of Sunitinib Malate Versus Sorafenib In Patients With Inoperable Liver Cancer (NCT NCT00699374)

Last Updated: 2013-01-14

Results Overview

Overall survival is the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1075 participants

Primary outcome timeframe

Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

Results posted on

2013-01-14

Participant Flow

One participant was randomized twice, once to the sorafenib arm and discontinued prior to receiving treatment and a second randomization to the sunitinib arm and dispensed treatment.

Participant milestones

Participant milestones
Measure	Sunitinib Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
Overall Study STARTED	530	544
Overall Study Treated	526	542
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	530	544

Reasons for withdrawal

Reasons for withdrawal
Measure	Sunitinib Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
Overall Study Death	93	83
Overall Study Adverse Event	70	67
Overall Study Global deterioration of health status	7	8
Overall Study Lost to Follow-up	3	5
Overall Study Withdrawal by Subject	34	44
Overall Study Objective progression or relapse	281	277
Overall Study Other	18	15
Overall Study Protocol Violation	2	6
Overall Study Study terminated by sponsor	13	28
Overall Study Randomized but not treated	4	2
Overall Study Died 28 days after last dose	5	9

Baseline Characteristics

Study Of Sunitinib Malate Versus Sorafenib In Patients With Inoperable Liver Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sunitinib n=530 Participants Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib n=544 Participants Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Total n=1074 Participants Total of all reporting groups
Age Continuous	58.1 Years STANDARD_DEVIATION 12.86 • n=5 Participants	58.5 Years STANDARD_DEVIATION 12.93 • n=7 Participants	58.3 Years STANDARD_DEVIATION 12.89 • n=5 Participants
Sex: Female, Male Female	94 Participants n=5 Participants	85 Participants n=7 Participants	179 Participants n=5 Participants
Sex: Female, Male Male	436 Participants n=5 Participants	459 Participants n=7 Participants	895 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

Population: Full Analysis Population, all randomized participants where participants were classifed according to the randomized treatment arm regardless of what treatment, if any, was received.

Overall survival is the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

Outcome measures

Outcome measures
Measure	Sunitinib n=530 Participants Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib n=388 Events Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
Overall Survival (OS)	34.3 Weeks Interval 31.9 to 39.9	43.9 Weeks Interval 38.1 to 48.7

SECONDARY outcome

Timeframe: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

Population: Full Analysis Population

The period from randomization until disease progression or death.

Outcome measures

Outcome measures
Measure	Sunitinib n=408 Events Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib n=433 Events Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
Progression-Free Survival (PFS)	15.3 Weeks Interval 12.1 to 17.7	12.6 Weeks Interval 12.1 to 17.3

SECONDARY outcome

Timeframe: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

Population: Full Analysis Population

Time in weeks from randomization to first documentation of objective tumor progression or death due to cancer, whichever comes first. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\])

Outcome measures

Outcome measures
Measure	Sunitinib n=365 Events Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib n=393 Events Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
Time to Tumor Progression (TTP)	17.7 Weeks Interval 13.6 to 18.0	15.4 Weeks Interval 12.3 to 18.1

SECONDARY outcome

Timeframe: Day 1 of each cycle

Population: Data were not collected per Amendment 2 to the protocol removing collection for this endpoint.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula assigns a utility value for each domain in the profile. Score is transformed and results in a score range -0.594 to 1.000; higher score indicates better health state.

Outcome measures

Outcome data not reported

Adverse Events

Sunitinib

Serious events: 240 serious events

Other events: 515 other events

Deaths: 0 deaths

Sorafenib

Serious events: 204 serious events

Other events: 531 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Serious adverse events
Measure	Sunitinib n=526 participants at risk Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib n=542 participants at risk Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
Hepatobiliary disorders Bile duct stone	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	1.9% 10/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 5/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Febrile neutropenia	0.57% 3/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukopenia	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	0.38% 2/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Splenic infarction	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	2.3% 12/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 2/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Bradycardia	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac arrest	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 2/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial infarction	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial ischaemia	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Supraventricular tachycardia	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachycardia	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Cataract	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Diabetic retinopathy	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal hernia	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	1.1% 6/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 5/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.38% 2/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 5/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ascites	2.3% 12/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 6/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Cheilitis	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	1.9% 10/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.7% 9/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Duodenal ulcer	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.37% 2/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Enteritis	0.38% 2/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Faeces discoloured	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric antral vascular ectasia	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric ulcer	0.38% 2/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.18% 1/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric varices haemorrhage	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastritis erosive	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastritis haemorrhagic	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.3% 12/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.74% 4/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.19% 1/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Sunitinib n=526 participants at risk Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.	Sorafenib n=542 participants at risk Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
Blood and lymphatic system disorders Anaemia	15.0% 79/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.7% 47/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukopenia	18.3% 96/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 37/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	22.6% 119/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.5% 19/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	32.3% 170/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.7% 69/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hypothyroidism	5.7% 30/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.3% 7/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	17.1% 90/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.3% 56/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	23.0% 121/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	19.4% 105/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	14.1% 74/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.4% 78/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ascites	14.4% 76/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.8% 64/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	17.1% 90/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.9% 81/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	47.1% 248/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	46.9% 254/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	10.1% 53/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.2% 39/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Mouth ulceration	5.3% 28/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 18/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	24.5% 129/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	17.2% 93/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	16.5% 87/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.8% 53/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	19.6% 103/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.3% 61/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	14.8% 78/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.1% 60/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	4.0% 21/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.5% 30/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Face oedema	6.7% 35/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 5/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	32.5% 171/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	21.2% 115/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Mucosal inflammation	12.4% 65/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.2% 39/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema	8.7% 46/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.2% 23/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	13.5% 71/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.5% 46/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pain	4.8% 25/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.4% 29/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	20.0% 105/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	18.6% 101/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hyperbilirubinaemia	11.2% 59/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.9% 43/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	11.4% 60/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.9% 70/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	16.0% 84/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	17.0% 92/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood bilirubin increased	5.7% 30/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.5% 30/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Gamma-glutamyltransferase increased	3.2% 17/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.2% 28/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Neutrophil count decreased	9.5% 50/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.74% 4/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Platelet count	5.5% 29/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.7% 9/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Platelet count decreased	12.4% 65/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 16/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight decreased	8.4% 44/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	21.2% 115/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count decreased	8.6% 45/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 5/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	44.3% 233/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	34.5% 187/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoalbuminaemia	8.9% 47/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.7% 42/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	8.7% 46/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.4% 40/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	2.7% 14/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.0% 27/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	9.1% 48/526 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.1% 17/542 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.