A Clinical Trial Comparing Efficacy And Safety Of Sunitinib Versus Placebo For TheTreatment Of Patients At High Risk Of Recurrent Renal Cell Cancer (S-TRAC)

• ClinicalTrials.gov Identifier: NCT00375674
• Recruitment Status: Completed
• First Posted: September 13, 2006
• Results First Posted: August 18, 2017
• Last Update Posted: September 21, 2018
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Kidney Neoplasms
• Interventions: Drug: Sunitinib malate; Other: Placebo
• Enrollment: 674

Participant Flow

Recruitment Details	Of 674 enrolled participants (615 in global cohort and 59 in china cohort), the results presented refers to the study conducted on 615 (intent-to-treat population) in 21 countries and were randomized to sunitinib and placebo for 9 cycles (1 cycle=42 days).
Pre-assignment Details	Screening: From Week 0 (nephrectomy surgery) to Week 11; in this period, echocardiogram/multi-gated acquisition, post-surgery imaging, histopathology, physical examination, laboratory tests, electrocardiogram and concomitant treatment were assessed. Randomization occurred not before 3 weeks post-nephrectomy & not after 12 weeks post-nephrectomy.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Period Title: Overall Study
Started	309	306
Intent-to-Treat Population [1]	309	306
As-Treated Population [2]	306 [3]	304 [4]
Completed	165	165
Not Completed	144	141
Reason Not Completed
Other	26	18
Death	67	76
Participants refused further follow-up	31	30
Lost to Follow-up	17	15
Enrolled but not treated	3	2
[1] All randomized participants, who received study drug/a different drug to which they were randomized; [2] All participants, who received at least 1 dose of study drug according to actual study treatment; [3] 3 were randomized but not treated: 2 refused treatment & 1 withdrew before receiving study drug; [4] 2 were randomized but not treated: 1 was screening failure & 1 discontinued due to new liver lesions

Baseline Characteristics

Arm/Group Title		Sunitinib	Placebo	Total
Arm/Group Description		Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Total of all reporting groups
Overall Number of Baseline Participants		309	306	615
Baseline Analysis Population Description		Intent to treat (ITT) population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	309 participants	306 participants	615 participants
		56.8 (10.6)	57.9 (10.6)	57.9 (10.6)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	309 participants	306 participants	615 participants
<=18 years		0	0	0
Between 18 and 65 years		233	224	457
>=65 years		76	82	158
Sex/Gender, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	309 participants	306 participants	615 participants
Female		87	77	164
Male		222	229	451

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review
Description	DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by blinded independent central review (BICR) or investigator assessment for respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for remainder of follow-up period unless the participant had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized.
Time Frame	Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later.

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed	309	306
Median (95% Confidence Interval); Unit of Measure: Number of years
	6.8 [1]; (5.8 to NA)	5.6; (3.8 to 6.6)

[1]

The upper limit of the 95% confidence interval of the median DFS on Sunitinib was not reached

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Superiority analysis
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.030
	Comments	[Not Specified]
	Method	Cox Proportional hazards model
	Comments	Based on the Cox Proportional hazards model stratified by UISS High-Risk Group.
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.761
	Confidence Interval	(2-Sided) 95%; 0.594 to 0.975
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population]
Description	DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by BICR or investigator assessment for the respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for the remainder of the follow-up period unless the participants had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized.
Time Frame	Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed	309	306
Median (95% Confidence Interval); Unit of Measure: Number of years
	6.5; (4.7 to 7.0)	4.5; (3.8 to 5.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Superiority analysis
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.077
	Comments	[Not Specified]
	Method	Cox Proportional hazards model
	Comments	Based on the Cox Proportional hazards model stratified by UISS High-Risk Group
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.811
	Confidence Interval	(2-Sided) 95%; 0.643 to 1.023
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population)
Description	OS was defined as the time from the date of randomization to the date of death due to any cause.
Time Frame	Every 12 weeks until the time for final analysis (up to data cut-off date: 30 April 2017; maximum exposure:14.9 months)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed	309	306
Median (95% Confidence Interval); Unit of Measure: Year
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Data was not estimable due to small number of participants with an event.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Placebo
	Comments	Hazard ratio was based on the Cox Proportional hazards model stratified by UISS High-Risk Group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.661
	Comments	[Not Specified]
	Method	Log-rank test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.929
	Confidence Interval	(2-Sided) 95%; 0.670 to 1.289
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
Description	TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent.
Time Frame	Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later

Outcome Measure Data

Analysis Population Description

The As-Treated (AT) population included all participants who received at least 1 dose of study drug with treatment assignments designated according to actual study treatment received. This population was the primary population for evaluating treatment administration/ compliance and safety.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed	306	304
Measure Type: Number; Unit of Measure: Number of participants
Participants With Adverse Events (AEs)	305	270
Participants With Serious Adverse Events (SAEs)	67	52
Participants With Grade 3 or 4 AEs	189	61
Participants With Grade 5 AEs	5	5
Participants Discontinued Due to AEs	86	16
Participants With Dose Reduced Due to AEs	106	6
Temporary Discontinuation Due to AEs	141	40

5. Secondary Outcome

Title	Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles)
Description	TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent.
Time Frame	Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later

Outcome Measure Data

Analysis Population Description

AT population: All participants who received at least 1 dose of study drug with treatment assignments designated according to actual study treatment received.

The numbers of participants analyzed were the participants with any adverse event of special interest (AESI) and that one participant could have reported more than one AESI

Arm/Group Title		Sunitinib	Placebo
Arm/Group Description:		Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed		306	304
Mean (Standard Deviation); Unit of Measure: Weeks
Benign Neoplasm of Thyroid Gland	Number Analyzed	0 participants	1 participants
			35.1
Goitre	Number Analyzed	0 participants	2 participants
			305.6 (97.08)
Hyperthyroidism	Number Analyzed	12 participants	2 participants
		23.2 (25.95)	110.8 (146.57)
Hypothyroidism	Number Analyzed	56 participants	4 participants
		46.9 (75.30)	58.0 (62.06)
Papillary Thyroid Cancer	Number Analyzed	0 participants	1 participants
			22.1
Thyroid Disorder	Number Analyzed	1 participants	0 participants
		19
Thyroid Mass	Number Analyzed	0 participants	1 participants
			20.4

6. Secondary Outcome

Title	Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores
Description	Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale, 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from "not at all" to "very much" to assess functioning & symptoms; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL & more severe for symptoms.
Time Frame	Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.

Arm/Group Title		Sunitinib	Placebo
Arm/Group Description:		Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed		309	306
Mean (Standard Error); Unit of Measure: Scores on scale
Cycle 1 (Baseline)	Number Analyzed	292 participants	288 participants
		74.83 (1.044)	75.61 (1.044)
Cycle 2	Number Analyzed	260 participants	274 participants
		69.71 (1.289)	75.49 (1.097)
Cycle 3	Number Analyzed	241 participants	265 participants
		69.67 (1.278)	74.09 (1.142)
Cycle 4	Number Analyzed	227 participants	249 participants
		66.52 (1.307)	74.93 (1.109)
Cycle 5	Number Analyzed	219 participants	234 participants
		68.34 (1.340)	74.61 (1.179)
Cycle 6	Number Analyzed	210 participants	231 participants
		66.27 (1.396)	75.69 (1.172)
Cycle 7	Number Analyzed	200 participants	220 participants
		67.42 (1.447)	73.98 (1.222)
Cycle 8	Number Analyzed	185 participants	212 participants
		68.33 (1.376)	74.49 (1.260)
Cycle 9	Number Analyzed	177 participants	203 participants
		68.31 (1.556)	74.06 (1.338)
End of treatment (EOT)	Number Analyzed	250 participants	250 participants
		64.43 (1.367)	73.37 (1.264)

7. Secondary Outcome

Title	PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison
Description	Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale & 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning). The questionnaire includes 28 items with 4-point Likert type responses from "not at all" to "very much" to assess functioning; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL.
Time Frame	Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed	309	306
Mean (95% Confidence Interval); Unit of Measure: Scores on scale
Physical	83.54; (82.40 to 84.68)	87.53; (86.42 to 88.64)
Role	78.94; (77.14 to 80.74)	85.46; (83.70 to 87.23)
Emotional	80.92; (79.58 to 82.27)	82.97; (81.66 to 84.29)
Cognitive	85.50; (84.17 to 86.83)	87.43; (86.13 to 88.73)
Social	80.62; (79.04 to 82.21)	87.99; (86.44 to 89.53)

8. Secondary Outcome

Title	PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison
Description	PROs assessed health-related QoL by using the EORTC QLQ-C30, which was a 30 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from "not at all" to "very much" to assess symptoms. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented more severe symptoms.
Time Frame	Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed	309	306
Mean (95% Confidence Interval); Unit of Measure: Scores on scale
Fatigue	29.94; (28.33 to 31.56)	21.74; (20.16 to 23.31)
Nausea and Vomiting	7.35; (6.38 to 8.33)	3.46; (2.51 to 4.41)
Pain	21.81; (20.10 to 23.52)	16.63; (14.96 to 18.30)
Dyspnoea	14.97; (13.38 to 16.57)	11.89; (10.33 to 13.45)
Insomnia	22.22; (20.26 to 24.19)	20.73; (18.81 to 22.65)
Appetite Loss	14.66; (13.12 to 16.21)	4.62; (3.11 to 6.13)
Constipation	11.24; (9.66 to 12.82)	9.83; (8.29 to 11.37)
Diarrhoea	19.25; (17.54 to 20.95)	7.25; (5.59 to 8.91)
Financial Difficulties	15.12; (13.42 to 16.82)	13.92; (12.26 to 15.59)

9. Secondary Outcome

Title	PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population
Description	Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. In this outcome measure, the first part with 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, & anxiety/depression) was used; a participant was asked to rate each state on a 3-level scale (1=no problem, 2=some problem, & 3=extreme problem); higher levels indicated greater severity/impairment. The published weights allowed the creation of a single summary score called the EQ-5D index, which ranged from -0.594 to 1; low scores represented a higher level of dysfunction & 1 as perfect health.
Time Frame	Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.

Arm/Group Title		Sunitinib	Placebo
Arm/Group Description:		Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed		309	306
Mean (Standard Error); Unit of Measure: Units on a scale
Cycle 1 (Baseline)	Number Analyzed	293 participants	287 participants
		0.84 (0.011)	0.83 (0.011)
Cycle 2	Number Analyzed	255 participants	271 participants
		0.83 (0.011)	0.84 (0.011)
Cycle 3	Number Analyzed	235 participants	267 participants
		0.80 (0.013)	0.82 (0.012)
Cycle 4	Number Analyzed	231 participants	245 participants
		0.77 (0.014)	0.84 (0.011)
Cycle 5	Number Analyzed	218 participants	230 participants
		0.77 (0.016)	0.84 (0.013)
Cycle 6	Number Analyzed	211 participants	234 participants
		0.78 (0.016)	0.85 (0.012)
Cycle 7	Number Analyzed	199 participants	216 participants
		0.77 (0.016)	0.83 (0.014)
Cycle 8	Number Analyzed	185 participants	207 participants
		0.80 (0.015)	0.84 (0.013)
Cycle 9	Number Analyzed	174 participants	202 participants
		0.81 (0.015)	0.85 (0.013)
EOT	Number Analyzed	250 participants	245 participants
		0.75 (0.017)	0.83 (0.015)

10. Secondary Outcome

Title	PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means
Description	Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. The first part assessed the current health state. In this outcome measure, the second part was applied to assess the general health status by using visual analog scale (EQ-5D VAS) which measured participant's self-rated health status on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame	Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.

Arm/Group Title		Sunitinib	Placebo
Arm/Group Description:		Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed		309	306
Mean (Standard Error); Unit of Measure: Units on a scale
Cycle 1 (Baseline)	Number Analyzed	293 participants	287 participants
		77.31 (0.999)	75.67 (1.080)
Cycle 2	Number Analyzed	261 participants	268 participants
		74.39 (1.188)	76.99 (1.080)
Cycle 3	Number Analyzed	234 participants	261 participants
		74.20 (1.093)	76.85 (1.122)
Cycle 4	Number Analyzed	231 participants	246 participants
		74.14 (1.118)	77.34 (1.115)
Cycle 5	Number Analyzed	218 participants	233 participants
		73.30 (1.220)	77.56 (1.212)
Cycle 6	Number Analyzed	211 participants	232 participants
		73.51 (1.250)	78.61 (1.130)
Cycle 7	Number Analyzed	199 participants	218 participants
		72.27 (1.267)	77.49 (1.180)
Cycle 8	Number Analyzed	186 participants	209 participants
		73.96 (1.226)	77.65 (1.213)
Cycle 9	Number Analyzed	174 participants	203 participants
		72.93 (1.424)	79.02 (1.168)
EOT	Number Analyzed	251 participants	246 participants
		71.79 (1.139)	76.93 (1.283)

11. Secondary Outcome

Title	Number of Participants With Tolerability Symptoms
Description	Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. This table provides the summary of discontinuations de to adverse events. Participants were counted only once in each row.
Time Frame	Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Sunitinib	Placebo
Arm/Group Description:	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
Overall Number of Participants Analyzed	309	306
Measure Type: Number; Unit of Measure: Number of participants
Palmar-plantar erythrodysaesthesia syndrome	13	0
Hypertension	6	0
Asthenia	4	0
Fatigue	3	1
Pulmonary embolism	3	1
Gastrooesophageal reflux disease	3	0
Ejection fraction decreased	2	1
Left ventricular dysfunction	2	1
Acute myocardial infarction	2	0
Blood creatinine increased	2	0
Dehydration	2	0
Dyspepsia	2	0
Proteinuria	2	0
Thrombocytopenia	2	0
Upper gastrointestinal haemorrhage	2	0
Vomiting	2	0
Electrocardiogram QT prolonged	1	1
Lethargy	1	1
Transient ischaemic attack	1	1
Depression	0	2
Abdominal pain	1	0
Abdominal pain upper	1	0
Acute kidney injury	1	0
Ageusia	1	0
Alanine aminotransferase increased	1	0
Anal inflammation	1	0
Anal pruritus	1	0
Aspartate aminotransferase increased	1	0
Atrial fibrillation	1	0
Atrial flutter	1	0
Diarrhoea	1	0
Disease progression	1	0
Dysgeusia	1	0
Electrocardiogram ST segment abnormal	1	0
Embolism venous	1	0
Eyelid oedema	1	0
Gastritis haemorrhagic	1	0
Glossodynia	1	0
Hepatic function abnormal	1	0
Hepatitis acute	1	0
Hypercreatininaemia	1	0
Hypertransaminasaemia	1	0
Hypothyroidism	1	0
Influenza like illness	1	0
Mental status changes	1	0
Mucosal inflammation	1	0
Myalgia	1	0
Myocardial infarction	1	0
Myocarditis	1	0
Necrosis	1	0
Nephrotic syndrome	1	0
Neutropenia	1	0
Oedema peripheral	1	0
Pancytopenia	1	0
Post procedural infection	1	0
Presyncope	1	0
Pyrexia	1	0
Stomatitis	1	0
Therapeutic response unexpected	1	0
Tremor	1	0
Vena cava thrombosis	1	0
Vertigo	1	0
Agitated depression	0	1
Angina unstable	0	1
Brain cancer metastatic	0	1
Hepatitis	0	1
Hypersensitivity	0	1
Metastases to lung	0	1
Mood altered	0	1
Renal impairment	0	1
Tinnitus	0	1

Adverse Events

Time Frame	Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post-treatment, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later.
Adverse Event Reporting Description	Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be "chronic" or "stable," whichever was later.
Arm/Group Title	Sunitinib	Placebo
Arm/Group Description	Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.	Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
All-Cause Mortality
	Sunitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	67/306 (21.90%)	76/304 (25.00%)
Serious Adverse Events
	Sunitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	67/306 (21.90%)	52/304 (17.11%)
Blood and lymphatic system disorders
Anaemia * 1	1/306 (0.33%)	0/304 (0.00%)
Leukopenia * 1	2/306 (0.65%)	0/304 (0.00%)
Lymphopenia * 1	1/306 (0.33%)	0/304 (0.00%)
Neutropenia * 1	2/306 (0.65%)	0/304 (0.00%)
Pancytopenia * 1	1/306 (0.33%)	0/304 (0.00%)
Thrombocytopenia * 1	7/306 (2.29%)	1/304 (0.33%)
Cardiac disorders
Acute coronary syndrome * 1	1/306 (0.33%)	0/304 (0.00%)
Acute myocardial infarction * 1	2/306 (0.65%)	1/304 (0.33%)
Angina pectoris * 1	0/306 (0.00%)	1/304 (0.33%)
Angina unstable * 1	0/306 (0.00%)	2/304 (0.66%)
Atrial fibrillation * 1	2/306 (0.65%)	1/304 (0.33%)
Atrial flutter * 1	1/306 (0.33%)	0/304 (0.00%)
Atrioventricular block * 1	0/306 (0.00%)	1/304 (0.33%)
Bradycardia * 1	0/306 (0.00%)	1/304 (0.33%)
Cardiac arrest * 1	1/306 (0.33%)	1/304 (0.33%)
Myocardial infarction * 1	3/306 (0.98%)	1/304 (0.33%)
Myocarditis * 1	1/306 (0.33%)	0/304 (0.00%)
Sinus tachycardia * 1	0/306 (0.00%)	1/304 (0.33%)
Ear and labyrinth disorders
Tympanic membrane perforation * 1	1/306 (0.33%)	0/304 (0.00%)
Vertigo * 1	1/306 (0.33%)	0/304 (0.00%)
Endocrine disorders
Hypothyroidism * 1	1/306 (0.33%)	0/304 (0.00%)
Eye disorders
Cataract * 1	1/306 (0.33%)	0/304 (0.00%)
Diplopia * 1	1/306 (0.33%)	0/304 (0.00%)
Vitreous haemorrhage * 1	1/306 (0.33%)	0/304 (0.00%)
Gastrointestinal disorders
Abdominal hernia * 1	0/306 (0.00%)	1/304 (0.33%)
Abdominal pain * 1	3/306 (0.98%)	1/304 (0.33%)
Diarrhoea * 1	2/306 (0.65%)	0/304 (0.00%)
Enterocutaneous fistula * 1	0/306 (0.00%)	1/304 (0.33%)
Gastric ulcer haemorrhage * 1	1/306 (0.33%)	0/304 (0.00%)
Gastritis haemorrhagic * 1	1/306 (0.33%)	0/304 (0.00%)
Gastrooesophageal reflux disease * 1	1/306 (0.33%)	0/304 (0.00%)
Haemorrhoidal haemorrhage * 1	1/306 (0.33%)	0/304 (0.00%)
Ileus * 1	0/306 (0.00%)	1/304 (0.33%)
Inguinal hernia * 1	1/306 (0.33%)	0/304 (0.00%)
Large intestine perforation * 1	0/306 (0.00%)	1/304 (0.33%)
Melaena * 1	0/306 (0.00%)	1/304 (0.33%)
Nausea * 1	2/306 (0.65%)	0/304 (0.00%)
Pancreatitis acute * 1	1/306 (0.33%)	0/304 (0.00%)
Proctitis * 1	1/306 (0.33%)	0/304 (0.00%)
Umbilical hernia * 1	0/306 (0.00%)	1/304 (0.33%)
Upper gastrointestinal haemorrhage * 1	2/306 (0.65%)	1/304 (0.33%)
Vomiting * 1	3/306 (0.98%)	0/304 (0.00%)
General disorders
Asthenia * 1	0/306 (0.00%)	1/304 (0.33%)
Chest pain * 1	2/306 (0.65%)	1/304 (0.33%)
Disease progression * 1	1/306 (0.33%)	0/304 (0.00%)
Malaise * 1	1/306 (0.33%)	0/304 (0.00%)
Mucosal inflammation * 1	2/306 (0.65%)	0/304 (0.00%)
Multiple organ dysfunction syndrome * 1	0/306 (0.00%)	1/304 (0.33%)
Pyrexia * 1	5/306 (1.63%)	0/304 (0.00%)
Hepatobiliary disorders
Acute hepatic failure * 1	1/306 (0.33%)	0/304 (0.00%)
Cholecystitis acute * 1	1/306 (0.33%)	1/304 (0.33%)
Cholelithiasis * 1	2/306 (0.65%)	0/304 (0.00%)
Hepatic function abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Hepatitis acute * 1	2/306 (0.65%)	0/304 (0.00%)
Hepatotoxicity * 1	0/306 (0.00%)	1/304 (0.33%)
Hypertransaminasaemia * 1	1/306 (0.33%)	0/304 (0.00%)
Infections and infestations
Bronchitis viral * 1	1/306 (0.33%)	0/304 (0.00%)
Cellulitis * 1	1/306 (0.33%)	1/304 (0.33%)
Herpes zoster * 1	0/306 (0.00%)	1/304 (0.33%)
Liver abscess * 1	1/306 (0.33%)	0/304 (0.00%)
Paronychia * 1	1/306 (0.33%)	0/304 (0.00%)
Peritonitis * 1	1/306 (0.33%)	0/304 (0.00%)
Peritonsillar abscess * 1	1/306 (0.33%)	0/304 (0.00%)
Pneumonia * 1	1/306 (0.33%)	1/304 (0.33%)
Pneumonia legionella * 1	1/306 (0.33%)	0/304 (0.00%)
Post procedural infection * 1	1/306 (0.33%)	0/304 (0.00%)
Pyelonephritis * 1	1/306 (0.33%)	0/304 (0.00%)
Respiratory tract infection * 1	0/306 (0.00%)	1/304 (0.33%)
Sepsis * 1	1/306 (0.33%)	0/304 (0.00%)
Septic shock * 1	1/306 (0.33%)	0/304 (0.00%)
Urinary tract infection * 1	1/306 (0.33%)	3/304 (0.99%)
Injury, poisoning and procedural complications
Arthropod bite * 1	0/306 (0.00%)	1/304 (0.33%)
Contusion * 1	0/306 (0.00%)	1/304 (0.33%)
Fall * 1	0/306 (0.00%)	1/304 (0.33%)
Femur fracture * 1	0/306 (0.00%)	1/304 (0.33%)
Head injury * 1	1/306 (0.33%)	0/304 (0.00%)
Hip fracture * 1	1/306 (0.33%)	0/304 (0.00%)
Incisional hernia * 1	1/306 (0.33%)	0/304 (0.00%)
Injury * 1	1/306 (0.33%)	1/304 (0.33%)
Meniscus injury * 1	1/306 (0.33%)	0/304 (0.00%)
Post procedural haemorrhage * 1	0/306 (0.00%)	1/304 (0.33%)
Road traffic accident * 1	1/306 (0.33%)	0/304 (0.00%)
Subdural haematoma * 1	1/306 (0.33%)	0/304 (0.00%)
Subdural haemorrhage * 1	1/306 (0.33%)	0/304 (0.00%)
Investigations
Alanine aminotransferase increased * 1	1/306 (0.33%)	0/304 (0.00%)
Aspartate aminotransferase increased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood creatinine increased * 1	0/306 (0.00%)	1/304 (0.33%)
C-reactive protein increased * 1	1/306 (0.33%)	0/304 (0.00%)
Ejection fraction decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Platelet count decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Metabolism and nutrition disorders
Cachexia * 1	0/306 (0.00%)	1/304 (0.33%)
Dehydration * 1	2/306 (0.65%)	0/304 (0.00%)
Failure to thrive * 1	0/306 (0.00%)	1/304 (0.33%)
Hyponatraemia * 1	1/306 (0.33%)	0/304 (0.00%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion * 1	1/306 (0.33%)	0/304 (0.00%)
Lumbar spinal stenosis * 1	0/306 (0.00%)	1/304 (0.33%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia * 1	1/306 (0.33%)	0/304 (0.00%)
Acute promyelocytic leukaemia * 1	0/306 (0.00%)	1/304 (0.33%)
Basal cell carcinoma * 1	0/306 (0.00%)	1/304 (0.33%)
Benign neoplasm of bladder * 1	0/306 (0.00%)	1/304 (0.33%)
Carcinoid tumour of the gastrointestinal tract * 1	0/306 (0.00%)	1/304 (0.33%)
Colon cancer * 1	1/306 (0.33%)	0/304 (0.00%)
Endometrial adenocarcinoma * 1	1/306 (0.33%)	0/304 (0.00%)
Hepatocellular carcinoma * 1	1/306 (0.33%)	0/304 (0.00%)
Intraductal proliferative breast lesion * 1	0/306 (0.00%)	1/304 (0.33%)
Lung adenocarcinoma * 1	0/306 (0.00%)	1/304 (0.33%)
Lung neoplasm malignant * 1	0/306 (0.00%)	1/304 (0.33%)
Metastases to lung * 1	0/306 (0.00%)	1/304 (0.33%)
Papillary thyroid cancer * 1	0/306 (0.00%)	1/304 (0.33%)
Prostate cancer * 1	1/306 (0.33%)	1/304 (0.33%)
Tumour haemorrhage * 1	0/306 (0.00%)	1/304 (0.33%)
Nervous system disorders
Axonal neuropathy * 1	1/306 (0.33%)	0/304 (0.00%)
Cerebral haematoma * 1	0/306 (0.00%)	1/304 (0.33%)
Cerebrovascular accident * 1	0/306 (0.00%)	2/304 (0.66%)
Headache * 1	1/306 (0.33%)	0/304 (0.00%)
Presyncope * 1	1/306 (0.33%)	0/304 (0.00%)
Transient ischaemic attack * 1	2/306 (0.65%)	1/304 (0.33%)
Psychiatric disorders
Agitated depression * 1	0/306 (0.00%)	1/304 (0.33%)
Depression * 1	0/306 (0.00%)	2/304 (0.66%)
Mental status changes * 1	1/306 (0.33%)	0/304 (0.00%)
Renal and urinary disorders
Acute kidney injury * 1	2/306 (0.65%)	0/304 (0.00%)
Albuminuria * 1	1/306 (0.33%)	0/304 (0.00%)
Haematuria * 1	1/306 (0.33%)	1/304 (0.33%)
Nephrotic syndrome * 1	1/306 (0.33%)	0/304 (0.00%)
Renal colic * 1	1/306 (0.33%)	0/304 (0.00%)
Renal failure * 1	2/306 (0.65%)	0/304 (0.00%)
Urinary incontinence * 1	0/306 (0.00%)	1/304 (0.33%)
Urinary retention * 1	1/306 (0.33%)	1/304 (0.33%)
Reproductive system and breast disorders
Menorrhagia * 1	1/306 (0.33%)	0/304 (0.00%)
Respiratory, thoracic and mediastinal disorders
Atelectasis * 1	0/306 (0.00%)	1/304 (0.33%)
Dyspnoea * 1	0/306 (0.00%)	2/304 (0.66%)
Haemoptysis * 1	0/306 (0.00%)	1/304 (0.33%)
Pulmonary embolism * 1	5/306 (1.63%)	1/304 (0.33%)
Respiratory acidosis * 1	0/306 (0.00%)	1/304 (0.33%)
Skin and subcutaneous tissue disorders
Rash * 1	1/306 (0.33%)	0/304 (0.00%)
Surgical and medical procedures
Gastrectomy * 1	0/306 (0.00%)	1/304 (0.33%)
Splenectomy * 1	0/306 (0.00%)	1/304 (0.33%)
Vascular disorders
Deep vein thrombosis * 1	1/306 (0.33%)	1/304 (0.33%)
Hypertension * 1	8/306 (2.61%)	2/304 (0.66%)
Orthostatic hypotension * 1	1/306 (0.33%)	0/304 (0.00%)
Peripheral arterial occlusive disease * 1	0/306 (0.00%)	1/304 (0.33%)
Vena cava thrombosis * 1	1/306 (0.33%)	0/304 (0.00%)
Venous thrombosis limb * 1	0/306 (0.00%)	1/304 (0.33%)
1 Term from vocabulary, MedDRA; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Sunitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	303/306 (99.02%)	270/304 (88.82%)
Blood and lymphatic system disorders
Anaemia * 1	33/306 (10.78%)	7/304 (2.30%)
Eosinopenia * 1	1/306 (0.33%)	0/304 (0.00%)
Hyperglobulinaemia * 1	0/306 (0.00%)	1/304 (0.33%)
Increased tendency to bruise * 1	1/306 (0.33%)	0/304 (0.00%)
Leukocytosis * 1	0/306 (0.00%)	1/304 (0.33%)
Leukopenia * 1	45/306 (14.71%)	2/304 (0.66%)
Lymphadenopathy * 1	2/306 (0.65%)	0/304 (0.00%)
Lymphopenia * 1	8/306 (2.61%)	1/304 (0.33%)
Monocytopenia * 1	1/306 (0.33%)	0/304 (0.00%)
Neutropenia * 1	70/306 (22.88%)	2/304 (0.66%)
Thrombocytopenia * 1	61/306 (19.93%)	4/304 (1.32%)
Erythropenia * 1	1/306 (0.33%)	0/304 (0.00%)
Cardiac disorders
Angina pectoris * 1	5/306 (1.63%)	1/304 (0.33%)
Aortic valve stenosis * 1	1/306 (0.33%)	0/304 (0.00%)
Arrhythmia * 1	2/306 (0.65%)	5/304 (1.64%)
Arrhythmia supraventricular * 1	0/306 (0.00%)	1/304 (0.33%)
Atrial fibrillation * 1	1/306 (0.33%)	5/304 (1.64%)
Bradycardia * 1	1/306 (0.33%)	1/304 (0.33%)
Bundle branch block left * 1	1/306 (0.33%)	0/304 (0.00%)
Cardiac failure * 1	0/306 (0.00%)	2/304 (0.66%)
Cardiovascular disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Conduction disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Diastolic dysfunction * 1	1/306 (0.33%)	0/304 (0.00%)
Extrasystoles * 1	1/306 (0.33%)	0/304 (0.00%)
Left ventricular dysfunction * 1	7/306 (2.29%)	3/304 (0.99%)
Left ventricular hypertrophy * 1	0/306 (0.00%)	1/304 (0.33%)
Mitral valve incompetence * 1	0/306 (0.00%)	1/304 (0.33%)
Mitral valve prolapse * 1	1/306 (0.33%)	0/304 (0.00%)
Myocardial ischaemia * 1	1/306 (0.33%)	0/304 (0.00%)
Myocarditis * 1	1/306 (0.33%)	0/304 (0.00%)
Palpitations * 1	1/306 (0.33%)	3/304 (0.99%)
Pericardial effusion * 1	2/306 (0.65%)	0/304 (0.00%)
Pericarditis * 1	0/306 (0.00%)	1/304 (0.33%)
Sinus bradycardia * 1	2/306 (0.65%)	2/304 (0.66%)
Supraventricular extrasystoles * 1	1/306 (0.33%)	2/304 (0.66%)
Tachycardia * 1	1/306 (0.33%)	0/304 (0.00%)
Tricuspid valve incompetence * 1	0/306 (0.00%)	1/304 (0.33%)
Ventricular extrasystoles * 1	1/306 (0.33%)	1/304 (0.33%)
Ventricular hypokinesia * 1	1/306 (0.33%)	0/304 (0.00%)
Congenital, familial and genetic disorders
Dermoid cyst * 1	0/306 (0.00%)	1/304 (0.33%)
Ear and labyrinth disorders
Deafness * 1	1/306 (0.33%)	1/304 (0.33%)
Deafness unilateral * 1	0/306 (0.00%)	1/304 (0.33%)
Ear discomfort * 1	1/306 (0.33%)	0/304 (0.00%)
Ear pain * 1	3/306 (0.98%)	1/304 (0.33%)
External ear pain * 1	0/306 (0.00%)	1/304 (0.33%)
Hypoacusis * 1	3/306 (0.98%)	0/304 (0.00%)
Meniere's disease * 1	0/306 (0.00%)	1/304 (0.33%)
Tinnitus * 1	5/306 (1.63%)	5/304 (1.64%)
Tympanic membrane perforation * 1	1/306 (0.33%)	0/304 (0.00%)
Vertigo * 1	8/306 (2.61%)	12/304 (3.95%)
Endocrine disorders
Goitre * 1	0/306 (0.00%)	2/304 (0.66%)
Hyperparathyroidism * 1	1/306 (0.33%)	0/304 (0.00%)
Hyperthyroidism * 1	12/306 (3.92%)	2/304 (0.66%)
Hypothyroidism * 1	56/306 (18.30%)	4/304 (1.32%)
Oestrogen deficiency * 1	0/306 (0.00%)	1/304 (0.33%)
Thyroid disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Thyroid mass * 1	0/306 (0.00%)	1/304 (0.33%)
Eye disorders
Blindness unilateral * 1	1/306 (0.33%)	0/304 (0.00%)
Cataract * 1	3/306 (0.98%)	1/304 (0.33%)
Cataract subcapsular * 1	1/306 (0.33%)	0/304 (0.00%)
Conjunctival haemorrhage * 1	2/306 (0.65%)	0/304 (0.00%)
Diplopia * 1	2/306 (0.65%)	0/304 (0.00%)
Dry eye * 1	4/306 (1.31%)	1/304 (0.33%)
Eye discharge * 1	1/306 (0.33%)	0/304 (0.00%)
Eye haemorrhage * 1	2/306 (0.65%)	0/304 (0.00%)
Eye inflammation * 1	0/306 (0.00%)	1/304 (0.33%)
Eye irritation * 1	5/306 (1.63%)	0/304 (0.00%)
Eye oedema * 1	7/306 (2.29%)	0/304 (0.00%)
Eye pain * 1	3/306 (0.98%)	0/304 (0.00%)
Eye pruritus * 1	1/306 (0.33%)	1/304 (0.33%)
Eye swelling * 1	2/306 (0.65%)	0/304 (0.00%)
Eyelash discolouration * 1	2/306 (0.65%)	0/304 (0.00%)
Eyelid bleeding * 1	1/306 (0.33%)	0/304 (0.00%)
Eyelid oedema * 1	21/306 (6.86%)	1/304 (0.33%)
Eyelid pain * 1	0/306 (0.00%)	1/304 (0.33%)
Glaucoma * 1	1/306 (0.33%)	1/304 (0.33%)
Lacrimal disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Lacrimal gland enlargement * 1	0/306 (0.00%)	1/304 (0.33%)
Lacrimation increased * 1	12/306 (3.92%)	1/304 (0.33%)
Ocular hyperaemia * 1	1/306 (0.33%)	0/304 (0.00%)
Ocular surface disease * 1	1/306 (0.33%)	0/304 (0.00%)
Oscillopsia * 1	1/306 (0.33%)	0/304 (0.00%)
Periorbital oedema * 1	7/306 (2.29%)	0/304 (0.00%)
Photophobia * 1	2/306 (0.65%)	0/304 (0.00%)
Photopsia * 1	0/306 (0.00%)	1/304 (0.33%)
Retinopathy hypertensive * 1	1/306 (0.33%)	0/304 (0.00%)
Vision blurred * 1	2/306 (0.65%)	3/304 (0.99%)
Visual acuity reduced * 1	1/306 (0.33%)	1/304 (0.33%)
Visual impairment * 1	4/306 (1.31%)	1/304 (0.33%)
Gastrointestinal disorders
Abdominal adhesions * 1	1/306 (0.33%)	0/304 (0.00%)
Abdominal discomfort * 1	8/306 (2.61%)	8/304 (2.63%)
Abdominal distension * 1	11/306 (3.59%)	4/304 (1.32%)
Abdominal hernia * 1	1/306 (0.33%)	2/304 (0.66%)
Abdominal pain * 1	42/306 (13.73%)	15/304 (4.93%)
Abdominal pain lower * 1	7/306 (2.29%)	1/304 (0.33%)
Abdominal pain upper * 1	40/306 (13.07%)	13/304 (4.28%)
Abdominal rigidity * 1	1/306 (0.33%)	0/304 (0.00%)
Abdominal tenderness * 1	1/306 (0.33%)	0/304 (0.00%)
Abnormal faeces * 1	2/306 (0.65%)	0/304 (0.00%)
Anal fissure * 1	2/306 (0.65%)	0/304 (0.00%)
Anal haemorrhage * 1	2/306 (0.65%)	0/304 (0.00%)
Anal inflammation * 1	6/306 (1.96%)	0/304 (0.00%)
Anal pruritus * 1	3/306 (0.98%)	0/304 (0.00%)
Anal skin tags * 1	1/306 (0.33%)	0/304 (0.00%)
Anorectal discomfort * 1	4/306 (1.31%)	1/304 (0.33%)
Anorectal disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Aphthous ulcer * 1	12/306 (3.92%)	2/304 (0.66%)
Bowel movement irregularity * 1	1/306 (0.33%)	0/304 (0.00%)
Breath odour * 1	0/306 (0.00%)	2/304 (0.66%)
Change of bowel habit * 1	1/306 (0.33%)	0/304 (0.00%)
Chapped lips * 1	2/306 (0.65%)	1/304 (0.33%)
Colitis * 1	1/306 (0.33%)	0/304 (0.00%)
Colitis ulcerative * 1	0/306 (0.00%)	1/304 (0.33%)
Constipation * 1	36/306 (11.76%)	32/304 (10.53%)
Dental caries * 1	4/306 (1.31%)	0/304 (0.00%)
Diverticulum intestinal * 1	0/306 (0.00%)	1/304 (0.33%)
Dry mouth * 1	14/306 (4.58%)	8/304 (2.63%)
Duodenal ulcer * 1	1/306 (0.33%)	0/304 (0.00%)
Duodenitis * 1	0/306 (0.00%)	1/304 (0.33%)
Duodenogastric reflux * 1	3/306 (0.98%)	0/304 (0.00%)
Dyspepsia * 1	82/306 (26.80%)	19/304 (6.25%)
Dysphagia * 1	15/306 (4.90%)	1/304 (0.33%)
Eructation * 1	4/306 (1.31%)	1/304 (0.33%)
Flatulence * 1	26/306 (8.50%)	14/304 (4.61%)
Frequent bowel movements * 1	1/306 (0.33%)	0/304 (0.00%)
Functional gastrointestinal disorder * 1	1/306 (0.33%)	1/304 (0.33%)
Gastric mucosa erythema * 1	0/306 (0.00%)	1/304 (0.33%)
Gastritis * 1	5/306 (1.63%)	4/304 (1.32%)
Gastrointestinal disorder * 1	1/306 (0.33%)	2/304 (0.66%)
Gastrointestinal dysplasia * 1	1/306 (0.33%)	0/304 (0.00%)
Gastrointestinal hypermotility * 1	2/306 (0.65%)	0/304 (0.00%)
Gastrointestinal motility disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Gastrointestinal obstruction * 1	0/306 (0.00%)	1/304 (0.33%)
Gastrointestinal pain * 1	0/306 (0.00%)	1/304 (0.33%)
Gastrooesophageal reflux disease * 1	27/306 (8.82%)	9/304 (2.96%)
Gingival bleeding * 1	9/306 (2.94%)	0/304 (0.00%)
Gingival oedema * 1	1/306 (0.33%)	0/304 (0.00%)
Gingival pain * 1	2/306 (0.65%)	1/304 (0.33%)
Gingival recession * 1	1/306 (0.33%)	0/304 (0.00%)
Gingival swelling * 1	2/306 (0.65%)	0/304 (0.00%)
Gingival ulceration * 1	1/306 (0.33%)	0/304 (0.00%)
Glossitis * 1	4/306 (1.31%)	1/304 (0.33%)
Glossodynia * 1	4/306 (1.31%)	0/304 (0.00%)
Haemorrhoidal haemorrhage * 1	2/306 (0.65%)	0/304 (0.00%)
Haemorrhoids * 1	12/306 (3.92%)	3/304 (0.99%)
Hiatus hernia * 1	1/306 (0.33%)	1/304 (0.33%)
Hyperchlorhydria * 1	3/306 (0.98%)	0/304 (0.00%)
Hypoaesthesia oral * 1	4/306 (1.31%)	0/304 (0.00%)
Impaired gastric emptying * 1	1/306 (0.33%)	0/304 (0.00%)
Inguinal hernia * 1	1/306 (0.33%)	0/304 (0.00%)
Large intestine polyp * 1	1/306 (0.33%)	0/304 (0.00%)
Lip disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Lip dry * 1	0/306 (0.00%)	1/304 (0.33%)
Lip ulceration * 1	1/306 (0.33%)	0/304 (0.00%)
Loose tooth * 1	1/306 (0.33%)	0/304 (0.00%)
Mouth cyst * 1	0/306 (0.00%)	1/304 (0.33%)
Mouth ulceration * 1	9/306 (2.94%)	3/304 (0.99%)
Nausea * 1	103/306 (33.66%)	42/304 (13.82%)
Odynophagia * 1	5/306 (1.63%)	0/304 (0.00%)
Oesophageal pain * 1	3/306 (0.98%)	0/304 (0.00%)
Oesophagitis * 1	14/306 (4.58%)	1/304 (0.33%)
Oral discomfort * 1	4/306 (1.31%)	0/304 (0.00%)
Oral disorder * 1	3/306 (0.98%)	0/304 (0.00%)
Oral mucosal blistering * 1	1/306 (0.33%)	0/304 (0.00%)
Oral mucosal erythema * 1	0/306 (0.00%)	1/304 (0.33%)
Oral pain * 1	7/306 (2.29%)	2/304 (0.66%)
Oral toxicity * 1	1/306 (0.33%)	0/304 (0.00%)
Palatal oedema * 1	1/306 (0.33%)	0/304 (0.00%)
Palatal swelling * 1	0/306 (0.00%)	1/304 (0.33%)
Pancreatic steatosis * 1	0/306 (0.00%)	1/304 (0.33%)
Perianal erythema * 1	1/306 (0.33%)	0/304 (0.00%)
Proctalgia * 1	7/306 (2.29%)	1/304 (0.33%)
Proctitis * 1	9/306 (2.94%)	1/304 (0.33%)
Rectal haemorrhage * 1	6/306 (1.96%)	1/304 (0.33%)
Regurgitation * 1	1/306 (0.33%)	0/304 (0.00%)
Salivary hypersecretion * 1	2/306 (0.65%)	0/304 (0.00%)
Sensitivity of teeth * 1	2/306 (0.65%)	1/304 (0.33%)
Stomatitis * 1	81/306 (26.47%)	13/304 (4.28%)
Swollen tongue * 1	1/306 (0.33%)	1/304 (0.33%)
Tongue disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Tongue oedema * 1	1/306 (0.33%)	0/304 (0.00%)
Tongue ulceration * 1	3/306 (0.98%)	1/304 (0.33%)
Tooth loss * 1	1/306 (0.33%)	0/304 (0.00%)
Toothache * 1	5/306 (1.63%)	3/304 (0.99%)
Vomiting * 1	55/306 (17.97%)	20/304 (6.58%)
Diarrhoea * 1	175/306 (57.19%)	65/304 (21.38%)
Gingival discomfort * 1	1/306 (0.33%)	0/304 (0.00%)
Tongue discomfort * 1	3/306 (0.98%)	0/304 (0.00%)
General disorders
Asthenia * 1	69/306 (22.55%)	36/304 (11.84%)
Chest discomfort * 1	4/306 (1.31%)	2/304 (0.66%)
Chest pain * 1	11/306 (3.59%)	13/304 (4.28%)
Chills * 1	10/306 (3.27%)	4/304 (1.32%)
Cyst * 1	1/306 (0.33%)	0/304 (0.00%)
Death * 1	1/306 (0.33%)	0/304 (0.00%)
Face oedema * 1	28/306 (9.15%)	1/304 (0.33%)
Facial pain * 1	1/306 (0.33%)	0/304 (0.00%)
Fatigue * 1	112/306 (36.60%)	74/304 (24.34%)
Feeling abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Feeling cold * 1	4/306 (1.31%)	2/304 (0.66%)
Feeling hot * 1	0/306 (0.00%)	2/304 (0.66%)
Feeling of body temperature change * 1	1/306 (0.33%)	0/304 (0.00%)
General physical health deterioration * 1	3/306 (0.98%)	2/304 (0.66%)
Generalised oedema * 1	1/306 (0.33%)	0/304 (0.00%)
Hernia * 1	1/306 (0.33%)	2/304 (0.66%)
Hypothermia * 1	1/306 (0.33%)	1/304 (0.33%)
Impaired healing * 1	1/306 (0.33%)	0/304 (0.00%)
Influenza like illness * 1	11/306 (3.59%)	5/304 (1.64%)
Infusion site extravasation * 1	0/306 (0.00%)	1/304 (0.33%)
Injection site haematoma * 1	1/306 (0.33%)	0/304 (0.00%)
Injection site inflammation * 1	0/306 (0.00%)	1/304 (0.33%)
Localised oedema * 1	2/306 (0.65%)	0/304 (0.00%)
Malaise * 1	6/306 (1.96%)	1/304 (0.33%)
Mucosal discolouration * 1	0/306 (0.00%)	1/304 (0.33%)
Mucosal dryness * 1	4/306 (1.31%)	1/304 (0.33%)
Mucosal induration * 1	1/306 (0.33%)	0/304 (0.00%)
Mucosal inflammation * 1	102/306 (33.33%)	25/304 (8.22%)
Necrosis * 1	1/306 (0.33%)	0/304 (0.00%)
Oedema * 1	10/306 (3.27%)	2/304 (0.66%)
Oedema mucosal * 1	1/306 (0.33%)	0/304 (0.00%)
Oedema peripheral * 1	24/306 (7.84%)	16/304 (5.26%)
Pain * 1	9/306 (2.94%)	9/304 (2.96%)
Peripheral swelling * 1	3/306 (0.98%)	0/304 (0.00%)
Pyrexia * 1	32/306 (10.46%)	17/304 (5.59%)
Secretion discharge * 1	1/306 (0.33%)	0/304 (0.00%)
Swelling * 1	1/306 (0.33%)	0/304 (0.00%)
Temperature intolerance * 1	4/306 (1.31%)	0/304 (0.00%)
Therapeutic response unexpected * 1	1/306 (0.33%)	0/304 (0.00%)
Xerosis * 1	0/306 (0.00%)	1/304 (0.33%)
Sensation of foreign body * 1	1/306 (0.33%)	0/304 (0.00%)
Hepatobiliary disorders
Cholecystitis * 1	1/306 (0.33%)	1/304 (0.33%)
Cholecystitis acute * 1	1/306 (0.33%)	0/304 (0.00%)
Cholelithiasis * 1	1/306 (0.33%)	1/304 (0.33%)
Hepatic steatosis * 1	0/306 (0.00%)	1/304 (0.33%)
Hepatitis * 1	0/306 (0.00%)	1/304 (0.33%)
Hepatitis acute * 1	1/306 (0.33%)	0/304 (0.00%)
Hepatotoxicity * 1	1/306 (0.33%)	0/304 (0.00%)
Hyperbilirubinaemia * 1	5/306 (1.63%)	2/304 (0.66%)
Hypertransaminasaemia * 1	2/306 (0.65%)	1/304 (0.33%)
Jaundice * 1	20/306 (6.54%)	0/304 (0.00%)
Liver disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Portal vein thrombosis * 1	0/306 (0.00%)	1/304 (0.33%)
Immune system disorders
Contrast media allergy * 1	0/306 (0.00%)	1/304 (0.33%)
Drug hypersensitivity * 1	1/306 (0.33%)	0/304 (0.00%)
Hypersensitivity * 1	3/306 (0.98%)	5/304 (1.64%)
Seasonal allergy * 1	1/306 (0.33%)	0/304 (0.00%)
Infections and infestations
Angular cheilitis * 1	0/306 (0.00%)	1/304 (0.33%)
Bronchitis * 1	6/306 (1.96%)	6/304 (1.97%)
Bronchitis viral * 1	1/306 (0.33%)	0/304 (0.00%)
Candida infection * 1	1/306 (0.33%)	0/304 (0.00%)
Cellulitis * 1	3/306 (0.98%)	0/304 (0.00%)
Conjunctivitis * 1	8/306 (2.61%)	4/304 (1.32%)
Cystitis * 1	3/306 (0.98%)	2/304 (0.66%)
Diverticulitis * 1	0/306 (0.00%)	1/304 (0.33%)
Ear infection * 1	2/306 (0.65%)	4/304 (1.32%)
Enteritis infectious * 1	1/306 (0.33%)	0/304 (0.00%)
Erysipelas * 1	1/306 (0.33%)	1/304 (0.33%)
Eye infection * 1	0/306 (0.00%)	2/304 (0.66%)
Folliculitis * 1	0/306 (0.00%)	1/304 (0.33%)
Fungal infection * 1	3/306 (0.98%)	0/304 (0.00%)
Fungal skin infection * 1	1/306 (0.33%)	2/304 (0.66%)
Gastroenteritis * 1	2/306 (0.65%)	1/304 (0.33%)
Gastroenteritis viral * 1	0/306 (0.00%)	2/304 (0.66%)
Genital candidiasis * 1	1/306 (0.33%)	0/304 (0.00%)
Genital herpes * 1	1/306 (0.33%)	0/304 (0.00%)
Gingivitis * 1	8/306 (2.61%)	0/304 (0.00%)
Helicobacter gastritis * 1	1/306 (0.33%)	0/304 (0.00%)
Herpes simplex * 1	1/306 (0.33%)	0/304 (0.00%)
Herpes virus infection * 1	5/306 (1.63%)	1/304 (0.33%)
Herpes zoster * 1	1/306 (0.33%)	0/304 (0.00%)
Hordeolum * 1	2/306 (0.65%)	0/304 (0.00%)
Influenza * 1	6/306 (1.96%)	3/304 (0.99%)
Liver abscess * 1	1/306 (0.33%)	0/304 (0.00%)
Localised infection * 1	3/306 (0.98%)	0/304 (0.00%)
Laryngitis * 1	1/306 (0.33%)	0/304 (0.00%)
Lower respiratory tract infection * 1	0/306 (0.00%)	4/304 (1.32%)
Lung infection * 1	1/306 (0.33%)	1/304 (0.33%)
Oral herpes * 1	7/306 (2.29%)	3/304 (0.99%)
Oral infection * 1	1/306 (0.33%)	0/304 (0.00%)
Nasopharyngitis * 1	15/306 (4.90%)	20/304 (6.58%)
Osteomyelitis * 1	1/306 (0.33%)	0/304 (0.00%)
Otitis externa * 1	1/306 (0.33%)	0/304 (0.00%)
Paronychia * 1	2/306 (0.65%)	0/304 (0.00%)
Periodontitis * 1	1/306 (0.33%)	0/304 (0.00%)
Pharyngitis * 1	6/306 (1.96%)	5/304 (1.64%)
Pharyngitis streptococcal * 1	0/306 (0.00%)	1/304 (0.33%)
Pilonidal cyst * 1	1/306 (0.33%)	0/304 (0.00%)
Pneumonia * 1	0/306 (0.00%)	1/304 (0.33%)
Postoperative wound infection * 1	0/306 (0.00%)	1/304 (0.33%)
Pulpitis dental * 1	1/306 (0.33%)	0/304 (0.00%)
Respiratory tract infection * 1	1/306 (0.33%)	2/304 (0.66%)
Retinitis * 1	0/306 (0.00%)	1/304 (0.33%)
Rhinitis * 1	7/306 (2.29%)	3/304 (0.99%)
Rhinolaryngitis * 1	1/306 (0.33%)	0/304 (0.00%)
Sinobronchitis * 1	1/306 (0.33%)	0/304 (0.00%)
Sinusitis * 1	4/306 (1.31%)	2/304 (0.66%)
Skin infection * 1	2/306 (0.65%)	0/304 (0.00%)
Staphylococcal scalded skin syndrome * 1	1/306 (0.33%)	0/304 (0.00%)
Tinea pedis * 1	1/306 (0.33%)	0/304 (0.00%)
Tooth abscess * 1	2/306 (0.65%)	0/304 (0.00%)
Tooth infection * 1	3/306 (0.98%)	2/304 (0.66%)
Tracheitis * 1	0/306 (0.00%)	2/304 (0.66%)
Upper respiratory tract infection * 1	6/306 (1.96%)	5/304 (1.64%)
Urinary tract infection * 1	7/306 (2.29%)	7/304 (2.30%)
Urogenital infection fungal * 1	1/306 (0.33%)	0/304 (0.00%)
Vaginal infection * 1	2/306 (0.65%)	1/304 (0.33%)
Viral hepatitis carrier * 1	0/306 (0.00%)	1/304 (0.33%)
Viral infection * 1	4/306 (1.31%)	0/304 (0.00%)
Viral labyrinthitis * 1	0/306 (0.00%)	1/304 (0.33%)
Vulvitis * 1	1/306 (0.33%)	0/304 (0.00%)
Vulvovaginal mycotic infection * 1	1/306 (0.33%)	1/304 (0.33%)
Wound infection * 1	0/306 (0.00%)	1/304 (0.33%)
Post procedural complication * 1	0/306 (0.00%)	1/304 (0.33%)
Peritonsillitis * 1	1/306 (0.33%)	0/304 (0.00%)
Injury, poisoning and procedural complications
Post procedural infection * 1	1/306 (0.33%)	0/304 (0.00%)
Burn oesophageal * 1	1/306 (0.33%)	1/304 (0.33%)
Burn oral cavity * 1	1/306 (0.33%)	0/304 (0.00%)
Chest injury * 1	0/306 (0.00%)	2/304 (0.66%)
Contusion * 1	7/306 (2.29%)	2/304 (0.66%)
Fall * 1	1/306 (0.33%)	2/304 (0.66%)
Incisional hernia * 1	0/306 (0.00%)	7/304 (2.30%)
Laceration * 1	1/306 (0.33%)	3/304 (0.99%)
Ligament injury * 1	0/306 (0.00%)	1/304 (0.33%)
Limb injury * 1	1/306 (0.33%)	2/304 (0.66%)
Patella fracture * 1	0/306 (0.00%)	1/304 (0.33%)
Procedural pain * 1	2/306 (0.65%)	5/304 (1.64%)
Rib fracture * 1	1/306 (0.33%)	0/304 (0.00%)
Skin abrasion * 1	1/306 (0.33%)	0/304 (0.00%)
Skin injury * 1	0/306 (0.00%)	1/304 (0.33%)
Soft tissue injury * 1	1/306 (0.33%)	0/304 (0.00%)
Stress fracture * 1	1/306 (0.33%)	1/304 (0.33%)
Wound complication * 1	0/306 (0.00%)	2/304 (0.66%)
Wound dehiscence * 1	1/306 (0.33%)	0/304 (0.00%)
Investigations
Alanine aminotransferase * 1	0/306 (0.00%)	1/304 (0.33%)
Alanine aminotransferase increased * 1	15/306 (4.90%)	3/304 (0.99%)
Amylase increased * 1	1/306 (0.33%)	0/304 (0.00%)
Aspartate aminotransferase * 1	0/306 (0.00%)	1/304 (0.33%)
Aspartate aminotransferase increased * 1	16/306 (5.23%)	2/304 (0.66%)
Basophil count increased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood albumin decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood alkaline phosphatase increased * 1	3/306 (0.98%)	1/304 (0.33%)
Blood bicarbonate increased * 1	3/306 (0.98%)	2/304 (0.66%)
Blood bilirubin increased * 1	4/306 (1.31%)	1/304 (0.33%)
Blood calcium decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood chloride decreased * 1	0/306 (0.00%)	1/304 (0.33%)
Blood chloride increased * 1	0/306 (0.00%)	1/304 (0.33%)
Blood cholesterol increased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood creatine abnormal * 1	0/306 (0.00%)	1/304 (0.33%)
Blood creatine increased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood creatine phosphokinase MB increased * 1	1/306 (0.33%)	1/304 (0.33%)
Blood creatine phosphokinase increased * 1	17/306 (5.56%)	18/304 (5.92%)
Blood creatinine increased * 1	21/306 (6.86%)	24/304 (7.89%)
Blood glucose increased * 1	4/306 (1.31%)	2/304 (0.66%)
Blood lactate dehydrogenase decreased * 1	0/306 (0.00%)	1/304 (0.33%)
Blood lactate dehydrogenase increased * 1	15/306 (4.90%)	3/304 (0.99%)
Blood magnesium decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood potassium decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Blood potassium increased * 1	0/306 (0.00%)	3/304 (0.99%)
Blood pressure diastolic increased * 1	1/306 (0.33%)	2/304 (0.66%)
Blood pressure increased * 1	6/306 (1.96%)	2/304 (0.66%)
Blood pressure orthostatic * 1	1/306 (0.33%)	0/304 (0.00%)
Blood pressure systolic increased * 1	1/306 (0.33%)	3/304 (0.99%)
Blood sodium decreased * 1	0/306 (0.00%)	1/304 (0.33%)
Blood thyroid stimulating hormone decreased * 1	6/306 (1.96%)	1/304 (0.33%)
Blood thyroid stimulating hormone increased * 1	23/306 (7.52%)	7/304 (2.30%)
Blood triglycerides increased * 1	0/306 (0.00%)	1/304 (0.33%)
Blood urea increased * 1	5/306 (1.63%)	7/304 (2.30%)
Blood uric acid increased * 1	3/306 (0.98%)	2/304 (0.66%)
Body temperature increased * 1	1/306 (0.33%)	0/304 (0.00%)
Cardiac murmur * 1	0/306 (0.00%)	2/304 (0.66%)
Cardiac stress test abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Chest X-ray abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Ejection fraction decreased * 1	3/306 (0.98%)	6/304 (1.97%)
Electrocardiogram QT interval abnormal * 1	0/306 (0.00%)	1/304 (0.33%)
Electrocardiogram QT prolonged * 1	4/306 (1.31%)	1/304 (0.33%)
Electrocardiogram ST segment abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Electrocardiogram ST segment depression * 1	1/306 (0.33%)	0/304 (0.00%)
Electrocardiogram ST segment elevation * 1	0/306 (0.00%)	1/304 (0.33%)
Electrocardiogram ST-T change * 1	1/306 (0.33%)	2/304 (0.66%)
Electrocardiogram T wave inversion * 1	1/306 (0.33%)	0/304 (0.00%)
Electrocardiogram T wave peaked * 1	1/306 (0.33%)	0/304 (0.00%)
Eosinophil count increased * 1	0/306 (0.00%)	2/304 (0.66%)
Gamma-glutamyltransferase increased * 1	2/306 (0.65%)	1/304 (0.33%)
Haemoglobin decreased * 1	9/306 (2.94%)	2/304 (0.66%)
Hepatic enzyme increased * 1	2/306 (0.65%)	2/304 (0.66%)
International normalised ratio increased * 1	1/306 (0.33%)	0/304 (0.00%)
Liver function test increased * 1	1/306 (0.33%)	0/304 (0.00%)
Low density lipoprotein increased * 1	1/306 (0.33%)	0/304 (0.00%)
Monocyte count increased * 1	1/306 (0.33%)	0/304 (0.00%)
Neutrophil count * 1	2/306 (0.65%)	0/304 (0.00%)
Neutrophil count decreased * 1	13/306 (4.25%)	3/304 (0.99%)
Platelet count * 1	1/306 (0.33%)	0/304 (0.00%)
Platelet count decreased * 1	8/306 (2.61%)	1/304 (0.33%)
Platelet count increased * 1	0/306 (0.00%)	2/304 (0.66%)
Prostatic specific antigen increased * 1	1/306 (0.33%)	2/304 (0.66%)
Protein total decreased * 1	3/306 (0.98%)	0/304 (0.00%)
Protein total increased * 1	1/306 (0.33%)	2/304 (0.66%)
Protein urine present * 1	2/306 (0.65%)	0/304 (0.00%)
QRS axis abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Red blood cell count increased * 1	0/306 (0.00%)	1/304 (0.33%)
Staphylococcus test positive * 1	1/306 (0.33%)	0/304 (0.00%)
Thyroid function test abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Thyroxine decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Thyroxine free decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Transaminases increased * 1	2/306 (0.65%)	0/304 (0.00%)
Troponin T increased * 1	1/306 (0.33%)	0/304 (0.00%)
Visual acuity tests * 1	1/306 (0.33%)	0/304 (0.00%)
Weight decreased * 1	14/306 (4.58%)	2/304 (0.66%)
Weight increased * 1	8/306 (2.61%)	18/304 (5.92%)
White blood cell count * 1	1/306 (0.33%)	0/304 (0.00%)
White blood cell count decreased * 1	15/306 (4.90%)	2/304 (0.66%)
Xanthochromia * 1	1/306 (0.33%)	0/304 (0.00%)
Urobilinogen urine increased * 1	1/306 (0.33%)	0/304 (0.00%)
Red blood cell count decreased * 1	1/306 (0.33%)	0/304 (0.00%)
Metabolism and nutrition disorders
Alkalosis * 1	1/306 (0.33%)	0/304 (0.00%)
Decreased appetite * 1	59/306 (19.28%)	16/304 (5.26%)
Diabetes mellitus * 1	1/306 (0.33%)	2/304 (0.66%)
Dyslipidaemia * 1	1/306 (0.33%)	0/304 (0.00%)
Fluid retention * 1	1/306 (0.33%)	0/304 (0.00%)
Gout * 1	4/306 (1.31%)	1/304 (0.33%)
Hypercalcaemia * 1	1/306 (0.33%)	1/304 (0.33%)
Hypercholesterolaemia * 1	3/306 (0.98%)	7/304 (2.30%)
Hypercreatininaemia * 1	2/306 (0.65%)	0/304 (0.00%)
Hyperglycaemia * 1	9/306 (2.94%)	11/304 (3.62%)
Hyperkalaemia * 1	1/306 (0.33%)	3/304 (0.99%)
Hypoglycaemia * 1	0/306 (0.00%)	3/304 (0.99%)
Hypocalcaemia * 1	3/306 (0.98%)	1/304 (0.33%)
Hyperlipidaemia * 1	2/306 (0.65%)	1/304 (0.33%)
Hypertriglyceridaemia * 1	3/306 (0.98%)	2/304 (0.66%)
Hyperuricaemia * 1	4/306 (1.31%)	5/304 (1.64%)
Hypoalbuminaemia * 1	3/306 (0.98%)	1/304 (0.33%)
Hypokalaemia * 1	3/306 (0.98%)	0/304 (0.00%)
Hypomagnesaemia * 1	1/306 (0.33%)	2/304 (0.66%)
Hyponatraemia * 1	3/306 (0.98%)	1/304 (0.33%)
Hypophagia * 1	1/306 (0.33%)	0/304 (0.00%)
Hypophosphataemia * 1	7/306 (2.29%)	3/304 (0.99%)
Hypoproteinaemia * 1	1/306 (0.33%)	0/304 (0.00%)
Hypovitaminosis * 1	1/306 (0.33%)	0/304 (0.00%)
Increased appetite * 1	0/306 (0.00%)	1/304 (0.33%)
Iron deficiency * 1	0/306 (0.00%)	1/304 (0.33%)
Malnutrition * 1	1/306 (0.33%)	0/304 (0.00%)
Type 2 diabetes mellitus * 1	0/306 (0.00%)	1/304 (0.33%)
Vitamin D deficiency * 1	1/306 (0.33%)	0/304 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	35/306 (11.44%)	29/304 (9.54%)
Arthritis * 1	1/306 (0.33%)	0/304 (0.00%)
Back pain * 1	28/306 (9.15%)	26/304 (8.55%)
Bone pain * 1	4/306 (1.31%)	8/304 (2.63%)
Bursitis * 1	0/306 (0.00%)	2/304 (0.66%)
Fibromyalgia * 1	1/306 (0.33%)	0/304 (0.00%)
Flank pain * 1	3/306 (0.98%)	4/304 (1.32%)
Groin pain * 1	3/306 (0.98%)	1/304 (0.33%)
Haemarthrosis * 1	0/306 (0.00%)	1/304 (0.33%)
Interspinous osteoarthritis * 1	0/306 (0.00%)	1/304 (0.33%)
Intervertebral disc disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Joint stiffness * 1	0/306 (0.00%)	1/304 (0.33%)
Joint swelling * 1	4/306 (1.31%)	2/304 (0.66%)
Limb discomfort * 1	1/306 (0.33%)	2/304 (0.66%)
Muscle fatigue * 1	2/306 (0.65%)	0/304 (0.00%)
Muscle mass * 1	0/306 (0.00%)	1/304 (0.33%)
Muscle spasms * 1	25/306 (8.17%)	13/304 (4.28%)
Muscular weakness * 1	3/306 (0.98%)	1/304 (0.33%)
Musculoskeletal discomfort * 1	0/306 (0.00%)	1/304 (0.33%)
Musculoskeletal disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Musculoskeletal pain * 1	13/306 (4.25%)	14/304 (4.61%)
Musculoskeletal stiffness * 1	2/306 (0.65%)	1/304 (0.33%)
Myalgia * 1	25/306 (8.17%)	15/304 (4.93%)
Myalgia intercostal * 1	0/306 (0.00%)	1/304 (0.33%)
Myositis * 1	1/306 (0.33%)	0/304 (0.00%)
Neck pain * 1	5/306 (1.63%)	5/304 (1.64%)
Nodal osteoarthritis * 1	0/306 (0.00%)	1/304 (0.33%)
Osteoarthritis * 1	4/306 (1.31%)	3/304 (0.99%)
Osteochondrosis * 1	0/306 (0.00%)	1/304 (0.33%)
Osteoporosis * 1	0/306 (0.00%)	1/304 (0.33%)
Osteoporosis postmenopausal * 1	1/306 (0.33%)	0/304 (0.00%)
Pain in extremity * 1	45/306 (14.71%)	20/304 (6.58%)
Periarthritis * 1	0/306 (0.00%)	1/304 (0.33%)
Rhabdomyolysis * 1	0/306 (0.00%)	1/304 (0.33%)
Soft tissue disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Spinal column stenosis * 1	0/306 (0.00%)	1/304 (0.33%)
Spinal osteoarthritis * 1	0/306 (0.00%)	2/304 (0.66%)
Spinal pain * 1	8/306 (2.61%)	2/304 (0.66%)
Synovial cyst * 1	1/306 (0.33%)	0/304 (0.00%)
Tendonitis * 1	0/306 (0.00%)	1/304 (0.33%)
Tenosynovitis * 1	1/306 (0.33%)	0/304 (0.00%)
Musculoskeletal chest pain * 1	7/306 (2.29%)	4/304 (1.32%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of bladder * 1	0/306 (0.00%)	1/304 (0.33%)
Benign neoplasm of thyroid gland * 1	0/306 (0.00%)	1/304 (0.33%)
Brain cancer metastatic * 1	0/306 (0.00%)	1/304 (0.33%)
Cancer pain * 1	0/306 (0.00%)	1/304 (0.33%)
Dysplastic naevus * 1	0/306 (0.00%)	1/304 (0.33%)
Haemangioma * 1	1/306 (0.33%)	0/304 (0.00%)
Lipoma * 1	1/306 (0.33%)	1/304 (0.33%)
Malignant melanoma * 1	0/306 (0.00%)	1/304 (0.33%)
Seborrhoeic keratosis * 1	0/306 (0.00%)	1/304 (0.33%)
Tumour haemorrhage * 1	1/306 (0.33%)	0/304 (0.00%)
Tumour pain * 1	0/306 (0.00%)	2/304 (0.66%)
Nervous system disorders
Ageusia * 1	21/306 (6.86%)	0/304 (0.00%)
Aphonia * 1	1/306 (0.33%)	1/304 (0.33%)
Balance disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Burning sensation * 1	1/306 (0.33%)	0/304 (0.00%)
Carotid arteriosclerosis * 1	1/306 (0.33%)	0/304 (0.00%)
Carotid artery stenosis * 1	0/306 (0.00%)	1/304 (0.33%)
Carpal tunnel syndrome * 1	0/306 (0.00%)	1/304 (0.33%)
Cerebral infarction * 1	0/306 (0.00%)	1/304 (0.33%)
Cerebrovascular accident * 1	1/306 (0.33%)	0/304 (0.00%)
Cognitive disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Dementia * 1	0/306 (0.00%)	1/304 (0.33%)
Depressed level of consciousness * 1	1/306 (0.33%)	0/304 (0.00%)
Disturbance in attention * 1	2/306 (0.65%)	1/304 (0.33%)
Dizziness * 1	23/306 (7.52%)	18/304 (5.92%)
Dizziness postural * 1	1/306 (0.33%)	0/304 (0.00%)
Dysaesthesia * 1	4/306 (1.31%)	1/304 (0.33%)
Dysgeusia * 1	103/306 (33.66%)	18/304 (5.92%)
Facial nerve disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Facial paralysis * 1	0/306 (0.00%)	1/304 (0.33%)
Formication * 1	0/306 (0.00%)	2/304 (0.66%)
Head discomfort * 1	1/306 (0.33%)	0/304 (0.00%)
Headache * 1	56/306 (18.30%)	36/304 (11.84%)
Hyperaesthesia * 1	5/306 (1.63%)	3/304 (0.99%)
Hypoaesthesia * 1	4/306 (1.31%)	1/304 (0.33%)
Hypogeusia * 1	2/306 (0.65%)	0/304 (0.00%)
Hypotonia * 1	1/306 (0.33%)	0/304 (0.00%)
Lethargy * 1	9/306 (2.94%)	9/304 (2.96%)
Loss of consciousness * 1	1/306 (0.33%)	0/304 (0.00%)
Memory impairment * 1	4/306 (1.31%)	3/304 (0.99%)
Migraine * 1	2/306 (0.65%)	0/304 (0.00%)
Muscle contractions involuntary * 1	1/306 (0.33%)	0/304 (0.00%)
Neuralgia * 1	2/306 (0.65%)	0/304 (0.00%)
Neuropathy peripheral * 1	7/306 (2.29%)	4/304 (1.32%)
Paraesthesia * 1	12/306 (3.92%)	11/304 (3.62%)
Parkinson's disease * 1	0/306 (0.00%)	1/304 (0.33%)
Peripheral motor neuropathy * 1	0/306 (0.00%)	1/304 (0.33%)
Peripheral sensory neuropathy * 1	2/306 (0.65%)	7/304 (2.30%)
Polyneuropathy * 1	1/306 (0.33%)	1/304 (0.33%)
Presyncope * 1	1/306 (0.33%)	0/304 (0.00%)
Restless legs syndrome * 1	1/306 (0.33%)	1/304 (0.33%)
Sciatica * 1	6/306 (1.96%)	0/304 (0.00%)
Seizure * 1	1/306 (0.33%)	0/304 (0.00%)
Sensory disturbance * 1	2/306 (0.65%)	0/304 (0.00%)
Sensory loss * 1	1/306 (0.33%)	0/304 (0.00%)
Somnolence * 1	1/306 (0.33%)	0/304 (0.00%)
Syncope * 1	2/306 (0.65%)	0/304 (0.00%)
Tongue paralysis * 1	0/306 (0.00%)	1/304 (0.33%)
Tremor * 1	3/306 (0.98%)	3/304 (0.99%)
Irregular sleep wake rhythm disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Psychiatric disorders
Affective disorder * 1	1/306 (0.33%)	2/304 (0.66%)
Agitated depression * 1	0/306 (0.00%)	1/304 (0.33%)
Agitation * 1	1/306 (0.33%)	0/304 (0.00%)
Anger * 1	0/306 (0.00%)	1/304 (0.33%)
Anxiety * 1	10/306 (3.27%)	14/304 (4.61%)
Apathy * 1	1/306 (0.33%)	0/304 (0.00%)
Confusional state * 1	1/306 (0.33%)	0/304 (0.00%)
Depressed mood * 1	3/306 (0.98%)	4/304 (1.32%)
Depression * 1	3/306 (0.98%)	10/304 (3.29%)
Insomnia * 1	30/306 (9.80%)	19/304 (6.25%)
Irritability * 1	5/306 (1.63%)	4/304 (1.32%)
Listless * 1	1/306 (0.33%)	0/304 (0.00%)
Mental disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Mood altered * 1	5/306 (1.63%)	3/304 (0.99%)
Nervousness * 1	4/306 (1.31%)	2/304 (0.66%)
Persecutory delusion * 1	1/306 (0.33%)	0/304 (0.00%)
Sleep disorder * 1	3/306 (0.98%)	1/304 (0.33%)
Stress * 1	1/306 (0.33%)	0/304 (0.00%)
Tension * 1	0/306 (0.00%)	1/304 (0.33%)
Renal and urinary disorders
Acute kidney injury * 1	1/306 (0.33%)	0/304 (0.00%)
Albuminuria * 1	0/306 (0.00%)	1/304 (0.33%)
Bladder disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Bladder pain * 1	0/306 (0.00%)	1/304 (0.33%)
Bladder spasm * 1	0/306 (0.00%)	1/304 (0.33%)
Chromaturia * 1	9/306 (2.94%)	0/304 (0.00%)
Dysuria * 1	1/306 (0.33%)	1/304 (0.33%)
Haematuria * 1	7/306 (2.29%)	5/304 (1.64%)
Nocturia * 1	1/306 (0.33%)	6/304 (1.97%)
Pollakiuria * 1	0/306 (0.00%)	3/304 (0.99%)
Proteinuria * 1	18/306 (5.88%)	9/304 (2.96%)
Pyelocaliectasis * 1	1/306 (0.33%)	0/304 (0.00%)
Renal cyst * 1	1/306 (0.33%)	0/304 (0.00%)
Renal failure * 1	1/306 (0.33%)	1/304 (0.33%)
Renal impairment * 1	1/306 (0.33%)	2/304 (0.66%)
Renal pain * 1	0/306 (0.00%)	2/304 (0.66%)
Urinary incontinence * 1	1/306 (0.33%)	1/304 (0.33%)
Urinary retention * 1	1/306 (0.33%)	0/304 (0.00%)
Urinary tract obstruction * 1	1/306 (0.33%)	0/304 (0.00%)
Reproductive system and breast disorders
Amenorrhoea * 1	1/306 (0.33%)	0/304 (0.00%)
Balanoposthitis * 1	2/306 (0.65%)	0/304 (0.00%)
Benign prostatic hyperplasia * 1	0/306 (0.00%)	3/304 (0.99%)
Breast engorgement * 1	1/306 (0.33%)	0/304 (0.00%)
Breast pain * 1	2/306 (0.65%)	0/304 (0.00%)
Erectile dysfunction * 1	2/306 (0.65%)	0/304 (0.00%)
Genital rash * 1	2/306 (0.65%)	0/304 (0.00%)
Gynaecomastia * 1	0/306 (0.00%)	3/304 (0.99%)
Haematospermia * 1	1/306 (0.33%)	0/304 (0.00%)
Breast tenderness * 1	0/306 (0.00%)	1/304 (0.33%)
Menometrorrhagia * 1	1/306 (0.33%)	0/304 (0.00%)
Menorrhagia * 1	1/306 (0.33%)	0/304 (0.00%)
Ovarian cyst * 1	2/306 (0.65%)	0/304 (0.00%)
Ovarian disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Pelvic pain * 1	2/306 (0.65%)	2/304 (0.66%)
Penile pain * 1	1/306 (0.33%)	0/304 (0.00%)
Prostatitis * 1	0/306 (0.00%)	1/304 (0.33%)
Prostatomegaly * 1	0/306 (0.00%)	1/304 (0.33%)
Scrotal erythema * 1	1/306 (0.33%)	0/304 (0.00%)
Scrotal pain * 1	2/306 (0.65%)	0/304 (0.00%)
Testicular pain * 1	0/306 (0.00%)	3/304 (0.99%)
Testicular swelling * 1	1/306 (0.33%)	0/304 (0.00%)
Testis discomfort * 1	1/306 (0.33%)	0/304 (0.00%)
Vulvovaginal dryness * 1	1/306 (0.33%)	0/304 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asphyxia * 1	0/306 (0.00%)	1/304 (0.33%)
Bronchial hyperreactivity * 1	0/306 (0.00%)	1/304 (0.33%)
Bronchial obstruction * 1	1/306 (0.33%)	0/304 (0.00%)
Cough * 1	22/306 (7.19%)	20/304 (6.58%)
Dry throat * 1	1/306 (0.33%)	2/304 (0.66%)
Dysphonia * 1	10/306 (3.27%)	5/304 (1.64%)
Dyspnoea * 1	17/306 (5.56%)	19/304 (6.25%)
Dyspnoea exertional * 1	5/306 (1.63%)	4/304 (1.32%)
Epistaxis * 1	55/306 (17.97%)	9/304 (2.96%)
Haemoptysis * 1	2/306 (0.65%)	1/304 (0.33%)
Hiccups * 1	2/306 (0.65%)	0/304 (0.00%)
Hydrothorax * 1	0/306 (0.00%)	1/304 (0.33%)
Laryngeal pain * 1	1/306 (0.33%)	0/304 (0.00%)
Lung disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Lung infiltration * 1	1/306 (0.33%)	0/304 (0.00%)
Nasal congestion * 1	3/306 (0.98%)	0/304 (0.00%)
Nasal discomfort * 1	2/306 (0.65%)	0/304 (0.00%)
Nasal disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Nasal dryness * 1	5/306 (1.63%)	1/304 (0.33%)
Nasal inflammation * 1	1/306 (0.33%)	0/304 (0.00%)
Oropharyngeal discomfort * 1	1/306 (0.33%)	0/304 (0.00%)
Oropharyngeal pain * 1	17/306 (5.56%)	10/304 (3.29%)
Pharyngeal erythema * 1	1/306 (0.33%)	0/304 (0.00%)
Pharyngeal ulceration * 1	1/306 (0.33%)	0/304 (0.00%)
Pleural effusion * 1	1/306 (0.33%)	0/304 (0.00%)
Pneumonitis * 1	0/306 (0.00%)	1/304 (0.33%)
Productive cough * 1	0/306 (0.00%)	5/304 (1.64%)
Pulmonary embolism * 1	1/306 (0.33%)	1/304 (0.33%)
Respiratory disorder * 1	0/306 (0.00%)	1/304 (0.33%)
Respiratory tract haemorrhage * 1	0/306 (0.00%)	1/304 (0.33%)
Rhinalgia * 1	1/306 (0.33%)	0/304 (0.00%)
Rhinitis allergic * 1	1/306 (0.33%)	0/304 (0.00%)
Rhinorrhoea * 1	4/306 (1.31%)	5/304 (1.64%)
Sneezing * 1	0/306 (0.00%)	1/304 (0.33%)
Sputum discoloured * 1	1/306 (0.33%)	2/304 (0.66%)
Tachypnoea * 1	1/306 (0.33%)	0/304 (0.00%)
Throat irritation * 1	0/306 (0.00%)	1/304 (0.33%)
Tonsillar hypertrophy * 1	1/306 (0.33%)	0/304 (0.00%)
Upper-airway cough syndrome * 1	1/306 (0.33%)	0/304 (0.00%)
Wheezing * 1	0/306 (0.00%)	2/304 (0.66%)
Skin and subcutaneous tissue disorders
Acne * 1	6/306 (1.96%)	1/304 (0.33%)
Alopecia * 1	26/306 (8.50%)	2/304 (0.66%)
Blister * 1	6/306 (1.96%)	1/304 (0.33%)
Cold sweat * 1	1/306 (0.33%)	0/304 (0.00%)
Dermal cyst * 1	0/306 (0.00%)	1/304 (0.33%)
Dermatitis * 1	5/306 (1.63%)	3/304 (0.99%)
Dry skin * 1	43/306 (14.05%)	17/304 (5.59%)
Dyshidrotic eczema * 1	0/306 (0.00%)	1/304 (0.33%)
Eczema * 1	5/306 (1.63%)	3/304 (0.99%)
Erythema * 1	13/306 (4.25%)	10/304 (3.29%)
Erythrosis * 1	0/306 (0.00%)	1/304 (0.33%)
Exfoliative rash * 1	5/306 (1.63%)	0/304 (0.00%)
Granuloma annulare * 1	1/306 (0.33%)	0/304 (0.00%)
Hair colour changes * 1	68/306 (22.22%)	7/304 (2.30%)
Hair growth abnormal * 1	2/306 (0.65%)	0/304 (0.00%)
Hair texture abnormal * 1	2/306 (0.65%)	0/304 (0.00%)
Hyperhidrosis * 1	1/306 (0.33%)	2/304 (0.66%)
Hyperkeratosis * 1	10/306 (3.27%)	2/304 (0.66%)
Ingrowing nail * 1	1/306 (0.33%)	0/304 (0.00%)
Keloid scar * 1	0/306 (0.00%)	1/304 (0.33%)
Macule * 1	1/306 (0.33%)	0/304 (0.00%)
Nail bed bleeding * 1	1/306 (0.33%)	0/304 (0.00%)
Nail discolouration * 1	1/306 (0.33%)	0/304 (0.00%)
Nail disorder * 1	6/306 (1.96%)	2/304 (0.66%)
Nail growth abnormal * 1	2/306 (0.65%)	0/304 (0.00%)
Nail toxicity * 1	3/306 (0.98%)	0/304 (0.00%)
Night sweats * 1	2/306 (0.65%)	2/304 (0.66%)
Palmar erythema * 1	2/306 (0.65%)	0/304 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome * 1	154/306 (50.33%)	31/304 (10.20%)
Panniculitis * 1	1/306 (0.33%)	0/304 (0.00%)
Papule * 1	1/306 (0.33%)	0/304 (0.00%)
Petechiae * 1	5/306 (1.63%)	0/304 (0.00%)
Photosensitivity reaction * 1	3/306 (0.98%)	2/304 (0.66%)
Pigmentation disorder * 1	2/306 (0.65%)	0/304 (0.00%)
Plantar erythema * 1	1/306 (0.33%)	0/304 (0.00%)
Pruritus * 1	21/306 (6.86%)	21/304 (6.91%)
Pruritus generalised * 1	2/306 (0.65%)	0/304 (0.00%)
Psoriasis * 1	2/306 (0.65%)	1/304 (0.33%)
Rash * 1	59/306 (19.28%)	29/304 (9.54%)
Rash erythematous * 1	1/306 (0.33%)	2/304 (0.66%)
Rash follicular * 1	1/306 (0.33%)	0/304 (0.00%)
Rash generalised * 1	2/306 (0.65%)	0/304 (0.00%)
Rash macular * 1	4/306 (1.31%)	1/304 (0.33%)
Rash maculo-papular * 1	1/306 (0.33%)	1/304 (0.33%)
Rash papular * 1	0/306 (0.00%)	1/304 (0.33%)
Rash vesicular * 1	1/306 (0.33%)	0/304 (0.00%)
Scar pain * 1	1/306 (0.33%)	7/304 (2.30%)
Seborrhoeic dermatitis * 1	1/306 (0.33%)	0/304 (0.00%)
Skin burning sensation * 1	1/306 (0.33%)	1/304 (0.33%)
Skin depigmentation * 1	2/306 (0.65%)	0/304 (0.00%)
Skin discolouration * 1	24/306 (7.84%)	1/304 (0.33%)
Skin disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Skin exfoliation * 1	11/306 (3.59%)	0/304 (0.00%)
Skin fissures * 1	3/306 (0.98%)	0/304 (0.00%)
Skin hyperpigmentation * 1	12/306 (3.92%)	2/304 (0.66%)
Skin hypertrophy * 1	0/306 (0.00%)	1/304 (0.33%)
Skin hypopigmentation * 1	9/306 (2.94%)	1/304 (0.33%)
Skin irritation * 1	1/306 (0.33%)	1/304 (0.33%)
Skin lesion * 1	9/306 (2.94%)	2/304 (0.66%)
Skin mass * 1	1/306 (0.33%)	1/304 (0.33%)
Skin odour abnormal * 1	1/306 (0.33%)	0/304 (0.00%)
Skin reaction * 1	1/306 (0.33%)	0/304 (0.00%)
Skin toxicity * 1	2/306 (0.65%)	0/304 (0.00%)
Splinter haemorrhages * 1	1/306 (0.33%)	0/304 (0.00%)
Swelling face * 1	5/306 (1.63%)	0/304 (0.00%)
Urticaria * 1	2/306 (0.65%)	1/304 (0.33%)
Urticaria thermal * 1	0/306 (0.00%)	1/304 (0.33%)
Yellow skin * 1	33/306 (10.78%)	2/304 (0.66%)
Social circumstances
Disability * 1	1/306 (0.33%)	0/304 (0.00%)
Walking disability * 1	1/306 (0.33%)	0/304 (0.00%)
Surgical and medical procedures
Abdominal hernia repair * 1	1/306 (0.33%)	0/304 (0.00%)
Cancer surgery * 1	1/306 (0.33%)	0/304 (0.00%)
Hysterectomy * 1	1/306 (0.33%)	0/304 (0.00%)
Injection * 1	1/306 (0.33%)	0/304 (0.00%)
Palatal operation * 1	1/306 (0.33%)	0/304 (0.00%)
Spleen operation * 1	1/306 (0.33%)	0/304 (0.00%)
Therapeutic procedure * 1	1/306 (0.33%)	0/304 (0.00%)
Tooth extraction * 1	2/306 (0.65%)	1/304 (0.33%)
Wisdom teeth removal * 1	1/306 (0.33%)	0/304 (0.00%)
Dental implantation * 1	0/306 (0.00%)	1/304 (0.33%)
Vascular disorders
Aortic aneurysm * 1	0/306 (0.00%)	1/304 (0.33%)
Arteriosclerosis * 1	0/306 (0.00%)	1/304 (0.33%)
Capillary disorder * 1	1/306 (0.33%)	0/304 (0.00%)
Embolism venous * 1	1/306 (0.33%)	0/304 (0.00%)
Endothelial dysfunction * 1	1/306 (0.33%)	0/304 (0.00%)
Flushing * 1	3/306 (0.98%)	1/304 (0.33%)
Haematoma * 1	3/306 (0.98%)	1/304 (0.33%)
Hot flush * 1	4/306 (1.31%)	3/304 (0.99%)
Hypertension * 1	112/306 (36.60%)	35/304 (11.51%)
Hypertensive crisis * 1	1/306 (0.33%)	1/304 (0.33%)
Hypotension * 1	4/306 (1.31%)	3/304 (0.99%)
Infarction * 1	1/306 (0.33%)	0/304 (0.00%)
Pallor * 1	1/306 (0.33%)	1/304 (0.33%)
Peripheral coldness * 1	2/306 (0.65%)	1/304 (0.33%)
Phlebitis * 1	1/306 (0.33%)	1/304 (0.33%)
Phlebolith * 1	0/306 (0.00%)	1/304 (0.33%)
Poor peripheral circulation * 1	1/306 (0.33%)	0/304 (0.00%)
1 Term from vocabulary, MedDRA; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 1800718 ext 1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Patel A, Ravaud A, Motzer RJ, Pantuck AJ, Staehler M, Escudier B, Martini JF, Lechuga M, Lin X, George DJ. Exploratory analysis of the platelet-to-lymphocyte ratio prognostic value in the adjuvant renal cell cancer setting. Future Oncol. 2021 Feb;17(4):403-409. doi: 10.2217/fon-2020-0652. Epub 2020 Oct 8.

Ouzaid I, Kammerer-Jacquet SF, Khene Z, Ravaud A, Patard JJ, Bensalah K, Rioux-Leclercq N. Exploring Biological Predictive Factors of Progression After Surgery in High-Risk Renal Cell Carcinoma: Results From the French Cohort of the Randomized S-TRAC Trial Patients. Front Surg. 2020 Jun 5;7:26. doi: 10.3389/fsurg.2020.00026. eCollection 2020.

Staehler M, Motzer RJ, George DJ, Pandha HS, Donskov F, Escudier B, Pantuck AJ, Patel A, DeAnnuntis L, Bhattacharyya H, Ramaswamy K, Zanotti G, Lin X, Lechuga M, Serfass L, Paty J, Ravaud A. Adjuvant sunitinib in patients with high-risk renal cell carcinoma: safety, therapy management, and patient-reported outcomes in the S-TRAC trial. Ann Oncol. 2018 Oct 1;29(10):2098-2104. doi: 10.1093/annonc/mdy329.

Rini BI, Escudier B, Martini JF, Magheli A, Svedman C, Lopatin M, Knezevic D, Goddard AD, Febbo PG, Li R, Lin X, Valota O, Staehler M, Motzer RJ, Ravaud A. Validation of the 16-Gene Recurrence Score in Patients with Locoregional, High-Risk Renal Cell Carcinoma from a Phase III Trial of Adjuvant Sunitinib. Clin Cancer Res. 2018 Sep 15;24(18):4407-4415. doi: 10.1158/1078-0432.CCR-18-0323. Epub 2018 May 17.

George DJ, Martini JF, Staehler M, Motzer RJ, Magheli A, Escudier B, Gerletti P, Li S, Casey M, Laguerre B, Pandha HS, Pantuck AJ, Patel A, Lechuga MJ, Ravaud A. Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study. Clin Cancer Res. 2018 Apr 1;24(7):1554-1561. doi: 10.1158/1078-0432.CCR-17-2822. Epub 2018 Jan 26.

Motzer RJ, Ravaud A, Patard JJ, Pandha HS, George DJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Casey M, Serfass L, Pantuck AJ, Staehler M. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results. Eur Urol. 2018 Jan;73(1):62-68. doi: 10.1016/j.eururo.2017.09.008. Epub 2017 Sep 28.

Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Martini JF, Ramaswamy K, Casey M, Staehler M, Patard JJ; S-TRAC Investigators. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. N Engl J Med. 2016 Dec 8;375(23):2246-2254. doi: 10.1056/NEJMoa1611406. Epub 2016 Oct 9.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00375674
• Other Study ID Numbers: A6181109; 2006-004024-37 ( EudraCT Number ); S-TRAC ( Other Identifier: Alias Study Number )
• First Submitted: September 12, 2006
• First Posted: September 13, 2006
• Results First Submitted: February 22, 2017
• Results First Posted: August 18, 2017
• Last Update Posted: September 21, 2018