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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
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
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
Hide 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
Arm/Group Title Sunitinib Placebo Total
Hide 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
Hide 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
1.Primary Outcome
Title Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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]
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
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
Hide 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%) 
Hide 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
Hide 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
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
Layout table for Results Point of Contact information
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):
Layout table for additonal information
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