ClinicalTrials.gov
ClinicalTrials.gov Menu

A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

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: NCT02130557
Recruitment Status : Active, not recruiting
First Posted : May 5, 2014
Results First Posted : November 14, 2018
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive
Interventions Drug: Bosutinib
Drug: Imatinib
Enrollment 536
Recruitment Details  
Pre-assignment Details Data reported was based on primary analysis date (11 August 2016).
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description Participants with Philadelphia chromosome-positive chronic myeloid leukemia (CML) received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment. Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Period Title: Overall Study
Started 268 268
Treated 268 265
mITT Population 246 241
Completed 0 0
Not Completed 268 268
Reason Not Completed
Randomized, not treated             0             3
Withdrawal by Subject             5             2
Lost to Follow-up             2             2
Deceased             1             6
Ongoing             260             255
Arm/Group Title Bosutinib Imatinib Total
Hide Arm/Group Description Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment. Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment. Total of all reporting groups
Overall Number of Baseline Participants 268 268 536
Hide Baseline Analysis Population Description
All randomized participants with study drug assignments designated according to initial randomization.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 268 participants 268 participants 536 participants
53.0
(18 to 84)
53.0
(19 to 84)
53.0
(18 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 268 participants 268 participants 536 participants
Female
112
  41.8%
113
  42.2%
225
  42.0%
Male
156
  58.2%
155
  57.8%
311
  58.0%
1.Primary Outcome
Title Percentage of Participants With Major Molecular Response (MMR) at Month 12
Hide Description MMR was defined as a ratio of breakpoint cluster region to abelson (Bcr-Abl/Abl) less than or equal to (<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to [>=] 3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts [>=3000 Abl required]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR).
Time Frame Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) population included all randomized participants with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies greater than (>) 0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47.2
(40.9 to 53.4)
36.9
(30.8 to 43.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments A total sample size of 500 Ph+ participants is required for the study to provide >= 90% power to detect at least 15% difference (assuming 25% in the imatinib vs 40% in the bosutinib arm) in the MMR rates at 12 months (48 weeks) with a 1-sided alpha of 2.5%, and 2 interim futility analyses at 33% and 66% of patients with adequate follow-up with early stopping for futility only (non-binding, O’Brien-Fleming analog beta spending function).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0100
Comments 1-sided p-value based on CMH test for general association between treatment and response with stratification by sokal risk group and region determined at time of randomization. Threshold for statistical significance: 1-sided 0.0125 significance level
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.547
Confidence Interval (2-Sided) 95%
1.072 to 2.233
Estimation Comments 95% CI for the odds ratio adjusted for sokal risk group and region are based on asymptotic wald confidence limits.
2.Secondary Outcome
Title Major Molecular Response (MMR) by Month 18
Hide Description

MMR was defined as a ratio of Bcr-Abl/Abl <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts [>=3000 Abl required]) by quantitative RT-qPCR.

It will be tested at the 1-sided significance level of 0.0125.

Time Frame up to Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The data for this outcome measure was immature as not all participants still on-treatment but without achieving MMR had reached the Month 18 visit at the time of data cut-off.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Duration of Major Molecular Response (MMR)
Hide Description It was defined as the time from the first date of MMR until the date of the confirmed loss of MMR or censoring. Confirmed Loss of MMR was Bcr-Abl/Abl IS ratio >0.1% in association with a >=5-fold increase in Bcr-Abl/Abl IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase or blast phase CML. Kaplan-meier analysis was used for determation of duration of MMR. Duration of response will be analyzed for responders only therefore duration of response will be excluded from the long-term family of secondary outcome measures.
Time Frame From the date of first MMR until the date of confirmed loss of MMR or censoring (up to 752 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization. N(overall number of participants analyzed)=number of participants evaluable for this outcome measure.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 142 122
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% C.I. could not be reached due to immaturity of events at the data cut off date.
4.Secondary Outcome
Title Percentage of Participants With Complete Cytogenetic Response (CCyR) by Month 12
Hide Description Complete Cytogenetic Response (CCyR) was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0 % Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available.
Time Frame up to Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
77.2
(72.0 to 82.5)
66.4
(60.4 to 72.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib, Imatinib
Comments If the primary analysis was significant, each endpoint of the short-term family (CCyR by Month 12) was tested via the Bonferroni’s procedure at the 1-sided 0.0125 significance level.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments 1-sided p-value based on CMH test for general association between treatment and response with stratification by sokal risk group and region determined at time of randomization. Threshold for statistical significance: 1-sided 0.0125 significance level
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.740
Confidence Interval (2-Sided) 95%
1.160 to 2.610
Estimation Comments 95% CI for the odds ratio adjusted for sokal risk group and region are based on asymptotic wald confidence limits.
5.Secondary Outcome
Title Duration of Complete Cytogenetic Response (CCyR)
Hide Description It was defined as the time from the first date of CCyR until the date of the confirmed loss of CCyR or censoring. Confirmed Loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to accelerated phase or blast phase CML. Kaplan meier analysis was used for the determination of duration of CCyR. Duration of response will be analyzed for responders only therefore duration of response will be excluded from the long-term family of secondary outcome measures.
Time Frame From the date of first CCyR until the date of confirmed loss of CCyR or censoring (up to 752 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization. N=number of participants evaluable for this outcome measure.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 197 175
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% C.I. was not estimable due to less number of participants who had event.
6.Secondary Outcome
Title Cumulative Incidence of Event Free Survival (EFS) Events at Month 12
Hide Description EFS was defined as the time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR [chronic phase, AP, or BP] confirmed by 2 assessments at least 4 weeks apart). Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of <100 metaphases confirmed by a follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS event at month 12 was adjusted for competing risk of treatment discontinuation without the event. The comparative analysis between the two arms for this member of the long-term secondary family will be done at the end of the study.
Time Frame Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.7
(1.8 to 6.7)
6.4
(3.7 to 10.0)
7.Secondary Outcome
Title Percentage of Participants Alive at Month 12
Hide Description OS was defined as the time (in months) from randomization to the occurrence of death due to any cause or censoring. Kaplan-meier analysis was used for determination of OS. The comparative analysis between the two arms for this member of the long-term secondary family will be done at the end of the study. Percentage of participants who were alive were estimated in this outcome measure.
Time Frame Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population included all randomized participants with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 246 241
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.6
(97.0 to 99.9)
97.9
(95.0 to 99.1)
8.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Complete Cytogenetic Response (CCyR)
Hide Description CCyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a BM aspirate. CCyR was achieved when there was 0 % Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. Trough plasma concentration of participants who had CCyR are presented in this outcome measure.
Time Frame Day 28, 56, 84
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here,"N" signifies number of participants evaluable for this outcome measure and "n" signifies participants evaluable at specified time points only.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 191
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
Day 28 Number Analyzed 181 participants
71.282  (46.0545)
Day 56 Number Analyzed 184 participants
73.069  (45.1349)
Day 84 Number Analyzed 184 participants
83.973  (64.3206)
9.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Major Molecular Response (MMR)
Hide Description MMR was defined as a ratio of Bcr-Abl/Abl <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts) by quantitative RT-qPCR. Trough plasma concentration of participants who had MMR are presented in this outcome measure.
Time Frame Day 28, 56, 84
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here,"N" signifies number of participants evaluable for this outcome measure and "n" signifies participants evaluable at specified time points only.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 141
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 28 Number Analyzed 140 participants
75.050  (51.9551)
Day 56 Number Analyzed 140 participants
78.437  (43.6019)
Day 84 Number Analyzed 141 participants
91.081  (72.1500)
10.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Presence of Grade 1 or Higher Adverse Events (AEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death. Trough plasma concentration of participants who had grade 1 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separately for each preferred term of AE.
Time Frame Day 28, 56, 84
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here,"N" signifies number of participants evaluable for this outcome measure and "n" signifies participants evaluable at specified time points only.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 177
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 28: Diarrhea Number Analyzed 177 participants
69.402  (55.5005)
Day 28: Thrombocytopenia Number Analyzed 60 participants
63.529  (40.9949)
Day 28: Rash Number Analyzed 84 participants
74.779  (60.6257)
Day 28: Nausea Number Analyzed 86 participants
66.011  (42.6437)
Day 28: Vomiting Number Analyzed 44 participants
71.684  (60.7208)
Day 56: Diarrhea Number Analyzed 172 participants
68.834  (42.6621)
Day 56: Thrombocytopenia Number Analyzed 61 participants
65.327  (43.2859)
Day 56: Rash Number Analyzed 84 participants
70.016  (38.7506)
Day 56: Nausea Number Analyzed 85 participants
61.626  (44.4007)
Day 56: Vomiting Number Analyzed 40 participants
65.980  (45.9064)
Day 84: Diarrhea Number Analyzed 165 participants
81.269  (64.6462)
Day 84: Thrombocytopenia Number Analyzed 63 participants
71.585  (33.6674)
Day 84: Rash Number Analyzed 85 participants
89.080  (69.5237)
Day 84: Nausea Number Analyzed 80 participants
77.702  (61.6179)
Day 84: Vomiting Number Analyzed 41 participants
86.949  (55.3041)
11.Other Pre-specified Outcome
Title Summary of Trough Plasma Concentration by Presence of Grade 3 or Higher Adverse Events (AEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death. Trough plasma concentration of participants who had grade 3 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separatley for each preferred term of AE.
Time Frame Day 28, 56, 84
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population included all enrolled participants who received at least 1 dose of bosutinib and had sufficient plasma results available. Here,"N" signifies number of participants evaluable for this outcome measure and "n" signifies participants evaluable at specified time points only.
Arm/Group Title Bosutinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 28: Diarrhea Number Analyzed 19 participants
87.769  (102.6181)
Day 28: Thrombocytopenia Number Analyzed 23 participants
49.220  (36.3461)
Day 28: Rash Number Analyzed 4 participants
71.150  (43.3246)
Day 28: Vomiting Number Analyzed 3 participants
14.663  (21.5799)
Day 56: Diarrhea Number Analyzed 16 participants
68.513  (45.2672)
Day 56: Thrombocytopenia Number Analyzed 24 participants
56.853  (34.3892)
Day 56: Rash Number Analyzed 4 participants
58.925  (18.8656)
Day 56: Vomiting Number Analyzed 1 participants
38.200 [1]   (NA)
Day 84: Diarrhea Number Analyzed 17 participants
76.782  (46.3006)
Day 84: Thrombocytopenia Number Analyzed 23 participants
67.623  (35.3084)
Day 84: Rash Number Analyzed 3 participants
83.967  (19.2542)
Day 84: Vomiting Number Analyzed 1 participants
12.400 [1]   (NA)
[1]
As only 1 participant was analyzed, standard deviation could not be calculated.
12.Other Pre-specified Outcome
Title Number of Participants With Vital Signs Abnormalities
Hide Description Criteria for vital signs abnormalities: systolic blood pressure (SBP) <80 millimeter of mercury (mmHg), >210 mmHg; diastolic blood pressure (DBP) <40 mmHg, >130 mmHg; heart rate <40 beats per minute (bpm), >150 bpm; temperature <32 degree celsius, >40 degree celsius.
Time Frame Baseline up to 752 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
13.Other Pre-specified Outcome
Title Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 4.03
Hide Description Laboratory parameters included hematological (haemoglobin, lymphocytes (absolute), neutrophils (absolute), platelets and leukocytes) and biochemistry (albumin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, amylase, bilirubin, creatinine kinase, calcium, creatinine, glucose, potassium, lipase, magnesium, phosphate, sodium, urate) parameters. Abnormalities in laboratory tests were graded by NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.
Time Frame Baseline up to 752 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
15
   5.6%
17
   6.4%
Grade 2
84
  31.3%
87
  32.8%
Grade 3
114
  42.5%
116
  43.8%
Grade 4
54
  20.1%
45
  17.0%
14.Other Pre-specified Outcome
Title Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Hide Description Criteria for ECG abnormalities : heart rate: increase of >15 bpm from baseline value and >=120 bpm, decrease of >15 bpm from baseline value and <=45 bpm; PR interval: change of >=20 msec from baseline value and >=220 milliseconds (msec); QRS interval >=120 msec; QTcB interval >500 msec, increase of >60 msec from baseline; QT interval using Fridericia’s correction (QTcF) >500 msec, increase of >60 msec from baseline, <=450 msec (Men) or <=470 msec (Women), >450 msec (Men) or >470 msec (Women).
Time Frame Baseline up to 752 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
6
   2.2%
6
   2.3%
15.Other Pre-specified Outcome
Title Number of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time Frame Baseline up to 752 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
38
  14.2%
28
  10.6%
16.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events By National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE version 4.03. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent events were events between first dose of study drug and up to 752 days that were absent before treatment that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 adverse event, only the maximum CTCAE was reported.
Time Frame Baseline up to 752 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description:
Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
Overall Number of Participants Analyzed 268 265
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
20
   7.5%
44
  16.6%
Grade 2
92
  34.3%
100
  37.7%
Grade 3
120
  44.8%
90
  34.0%
Grade 4
30
  11.2%
19
   7.2%
Grade 5
1
   0.4%
4
   1.5%
Time Frame Baseline up to 752 days
Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
 
Arm/Group Title Bosutinib Imatinib
Hide Arm/Group Description Participants with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment. Participants with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Participants who completed the core treatment period, entered into extension period and received same treatment.
All-Cause Mortality
Bosutinib Imatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   0/268 (0.00%)   4/265 (1.51%) 
Show Serious Adverse Events Hide Serious Adverse Events
Bosutinib Imatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   54/268 (20.15%)   45/265 (16.98%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/268 (0.37%)  3/265 (1.13%) 
Thrombocytopenia * 1  1/268 (0.37%)  1/265 (0.38%) 
Febrile neutropenia * 1  0/268 (0.00%)  2/265 (0.75%) 
Cardiac disorders     
Atrial fibrillation * 1  1/268 (0.37%)  1/265 (0.38%) 
Myocardial ischaemia * 1  2/268 (0.75%)  0/265 (0.00%) 
Acute coronary syndrome * 1  1/268 (0.37%)  0/265 (0.00%) 
Angina pectoris * 1  1/268 (0.37%)  0/265 (0.00%) 
Coronary artery disease * 1  1/268 (0.37%)  0/265 (0.00%) 
Coronary artery occlusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Pericardial effusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Supraventricular tachycardia * 1  1/268 (0.37%)  0/265 (0.00%) 
Ear and labyrinth disorders     
Vertigo positional * 1  1/268 (0.37%)  0/265 (0.00%) 
Eye disorders     
Retinal vein occlusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastrointestinal disorders     
Diarrhoea * 1  3/268 (1.12%)  1/265 (0.38%) 
Gastritis * 1  1/268 (0.37%)  1/265 (0.38%) 
Gastrointestinal necrosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Abdominal pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Colitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Diverticulum intestinal * 1  1/268 (0.37%)  0/265 (0.00%) 
Duodenal ulcer * 1  1/268 (0.37%)  0/265 (0.00%) 
Food poisoning * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastric ulcer * 1  0/268 (0.00%)  1/265 (0.38%) 
Gastrointestinal haemorrhage * 1  0/268 (0.00%)  1/265 (0.38%) 
Haemorrhoids * 1  1/268 (0.37%)  0/265 (0.00%) 
Pancreatitis acute * 1  1/268 (0.37%)  0/265 (0.00%) 
General disorders     
Pyrexia * 1  4/268 (1.49%)  1/265 (0.38%) 
General physical health deterioration * 1  0/268 (0.00%)  1/265 (0.38%) 
Hyperthermia * 1  0/268 (0.00%)  1/265 (0.38%) 
Implant site haematoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Non-cardiac chest pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Hepatobiliary disorders     
Hepatitis * 1  2/268 (0.75%)  0/265 (0.00%) 
Hepatotoxicity * 1  2/268 (0.75%)  0/265 (0.00%) 
Cholecystitis acute * 1  1/268 (0.37%)  0/265 (0.00%) 
Drug-induced liver injury * 1  1/268 (0.37%)  0/265 (0.00%) 
Infections and infestations     
Pneumonia * 1  4/268 (1.49%)  3/265 (1.13%) 
Gastroenteritis * 1  5/268 (1.87%)  1/265 (0.38%) 
Cellulitis * 1  1/268 (0.37%)  2/265 (0.75%) 
Sepsis * 1  0/268 (0.00%)  2/265 (0.75%) 
Subcutaneous abscess * 1  0/268 (0.00%)  2/265 (0.75%) 
Urinary tract infection * 1  0/268 (0.00%)  2/265 (0.75%) 
Abscess limb * 1  0/268 (0.00%)  1/265 (0.38%) 
Appendicitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Bronchitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Candida pneumonia * 1  1/268 (0.37%)  0/265 (0.00%) 
Infective pericardial effusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Influenza * 1  0/268 (0.00%)  1/265 (0.38%) 
Liver abscess * 1  0/268 (0.00%)  1/265 (0.38%) 
Lower respiratory tract infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Necrotising fasciitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Orchitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Periorbital cellulitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Respiratory tract infection viral * 1  0/268 (0.00%)  1/265 (0.38%) 
Splenic infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Upper respiratory tract infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Neutropenic infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Injury, poisoning and procedural complications     
Fall * 1  1/268 (0.37%)  0/265 (0.00%) 
Post procedural haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Road traffic accident * 1  1/268 (0.37%)  0/265 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  3/268 (1.12%)  0/265 (0.00%) 
Platelet count decreased * 1  2/268 (0.75%)  0/265 (0.00%) 
Aspartate aminotransferase increased * 1  2/268 (0.75%)  0/265 (0.00%) 
Blood creatine phosphokinase increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Blood sodium decreased * 1  0/268 (0.00%)  1/265 (0.38%) 
Transaminases increased * 1  1/268 (0.37%)  0/265 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/268 (0.37%)  0/265 (0.00%) 
Tumour lysis syndrome * 1  1/268 (0.37%)  0/265 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteochondrosis * 1  1/268 (0.37%)  1/265 (0.38%) 
Back pain * 1  0/268 (0.00%)  1/265 (0.38%) 
Arthralgia * 1  1/268 (0.37%)  0/265 (0.00%) 
Musculoskeletal chest pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Chronic myeloid leukaemia * 1  0/268 (0.00%)  1/265 (0.38%) 
Colon cancer * 1  1/268 (0.37%)  0/265 (0.00%) 
Invasive ductal breast carcinoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Lung neoplasm malignant * 1  1/268 (0.37%)  0/265 (0.00%) 
Myelodysplastic syndrome * 1  1/268 (0.37%)  0/265 (0.00%) 
Prostate cancer * 1  0/268 (0.00%)  1/265 (0.38%) 
Prostatic adenoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Rectal cancer * 1  1/268 (0.37%)  0/265 (0.00%) 
Transitional cell carcinoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Nervous system disorders     
Cerebrovascular accident * 1  0/268 (0.00%)  1/265 (0.38%) 
Headache * 1  1/268 (0.37%)  0/265 (0.00%) 
Syncope * 1  0/268 (0.00%)  1/265 (0.38%) 
Renal and urinary disorders     
Calculus bladder * 1  0/268 (0.00%)  1/265 (0.38%) 
Nephrotic syndrome * 1  0/268 (0.00%)  1/265 (0.38%) 
Ureterolithiasis * 1  0/268 (0.00%)  1/265 (0.38%) 
Urinary incontinence * 1  0/268 (0.00%)  1/265 (0.38%) 
Urinary retention * 1  0/268 (0.00%)  1/265 (0.38%) 
Haematuria * 1  2/268 (0.75%)  0/265 (0.00%) 
Reproductive system and breast disorders     
Prostatic dysplasia * 1  0/268 (0.00%)  1/265 (0.38%) 
Uterine haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  1/268 (0.37%)  1/265 (0.38%) 
Pleural effusion * 1  1/268 (0.37%)  1/265 (0.38%) 
Pneumothorax * 1  1/268 (0.37%)  0/265 (0.00%) 
Chronic obstructive pulmonary disease * 1  0/268 (0.00%)  1/265 (0.38%) 
Pulmonary hypertension * 1  1/268 (0.37%)  0/265 (0.00%) 
Pulmonary oedema * 1  1/268 (0.37%)  0/265 (0.00%) 
Pulmonary toxicity * 1  0/268 (0.00%)  1/265 (0.38%) 
Respiratory failure * 1  1/268 (0.37%)  0/265 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema * 1  0/268 (0.00%)  2/265 (0.75%) 
Dermatitis allergic * 1  1/268 (0.37%)  0/265 (0.00%) 
Lichen planus * 1  0/268 (0.00%)  1/265 (0.38%) 
Rash maculo-papular * 1  1/268 (0.37%)  0/265 (0.00%) 
Swelling face * 1  0/268 (0.00%)  1/265 (0.38%) 
Vascular disorders     
Hypertensive crisis * 1  1/268 (0.37%)  0/265 (0.00%) 
Hypotension * 1  0/268 (0.00%)  1/265 (0.38%) 
Hypovolaemic shock * 1  1/268 (0.37%)  0/265 (0.00%) 
1
Term from vocabulary, MedDRA v19.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Bosutinib Imatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   263/268 (98.13%)   257/265 (96.98%) 
Blood and lymphatic system disorders     
Thrombocytopenia * 1  63/268 (23.51%)  32/265 (12.08%) 
Anaemia * 1  52/268 (19.40%)  47/265 (17.74%) 
Neutropenia * 1  26/268 (9.70%)  44/265 (16.60%) 
Leukopenia * 1  9/268 (3.36%)  15/265 (5.66%) 
Lymphopenia * 1  8/268 (2.99%)  3/265 (1.13%) 
Leukocytosis * 1  7/268 (2.61%)  4/265 (1.51%) 
Increased tendency to bruise * 1  2/268 (0.75%)  0/265 (0.00%) 
Thrombocytosis * 1  2/268 (0.75%)  5/265 (1.89%) 
Haemorrhagic anaemia * 1  1/268 (0.37%)  0/265 (0.00%) 
Iron deficiency anaemia * 1  1/268 (0.37%)  1/265 (0.38%) 
Lymphadenopathy * 1  1/268 (0.37%)  1/265 (0.38%) 
Lymphocytosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Mastocytosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Microcytosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Normochromic normocytic anaemia * 1  1/268 (0.37%)  0/265 (0.00%) 
Pancytopenia * 1  1/268 (0.37%)  1/265 (0.38%) 
Eosinophilia * 1  0/268 (0.00%)  1/265 (0.38%) 
Granulocytopenia * 1  0/268 (0.00%)  2/265 (0.75%) 
Monocytopenia * 1  0/268 (0.00%)  1/265 (0.38%) 
Spontaneous haematoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Cardiac disorders     
Palpitations * 1  5/268 (1.87%)  8/265 (3.02%) 
Sinus bradycardia * 1  4/268 (1.49%)  0/265 (0.00%) 
Atrial fibrillation * 1  3/268 (1.12%)  1/265 (0.38%) 
Angina pectoris * 1  3/268 (1.12%)  1/265 (0.38%) 
Bradycardia * 1  2/268 (0.75%)  0/265 (0.00%) 
Myocardial ischaemia * 1  2/268 (0.75%)  0/265 (0.00%) 
Diastolic dysfunction * 1  1/268 (0.37%)  0/265 (0.00%) 
Extrasystoles * 1  1/268 (0.37%)  0/265 (0.00%) 
Pericardial effusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Supraventricular extrasystoles * 1  1/268 (0.37%)  0/265 (0.00%) 
Supraventricular tachycardia * 1  1/268 (0.37%)  1/265 (0.38%) 
Tachycardia * 1  1/268 (0.37%)  2/265 (0.75%) 
Ventricular extrasystoles * 1  1/268 (0.37%)  1/265 (0.38%) 
Bundle branch block right * 1  0/268 (0.00%)  1/265 (0.38%) 
Left ventricular hypertrophy * 1  0/268 (0.00%)  1/265 (0.38%) 
Sinus tachycardia * 1  0/268 (0.00%)  1/265 (0.38%) 
Tricuspid valve incompetence * 1  0/268 (0.00%)  1/265 (0.38%) 
Congenital, familial and genetic disorders     
Trisomy 8 * 1  1/268 (0.37%)  0/265 (0.00%) 
Cytogenetic abnormality * 1  0/268 (0.00%)  1/265 (0.38%) 
Ear and labyrinth disorders     
Ear pain * 1  5/268 (1.87%)  2/265 (0.75%) 
Tinnitus * 1  5/268 (1.87%)  1/265 (0.38%) 
Vertigo * 1  3/268 (1.12%)  5/265 (1.89%) 
Cerumen impaction * 1  1/268 (0.37%)  0/265 (0.00%) 
Deafness * 1  1/268 (0.37%)  1/265 (0.38%) 
Inner ear inflammation * 1  1/268 (0.37%)  0/265 (0.00%) 
Vertigo positional * 1  1/268 (0.37%)  0/265 (0.00%) 
Hypoacusis * 1  0/268 (0.00%)  1/265 (0.38%) 
Endocrine disorders     
Hypothyroidism * 1  2/268 (0.75%)  0/265 (0.00%) 
Hyperparathyroidism * 1  1/268 (0.37%)  0/265 (0.00%) 
Thyroid disorder * 1  1/268 (0.37%)  0/265 (0.00%) 
Thyroid mass * 1  0/268 (0.00%)  1/265 (0.38%) 
Eye disorders     
Eye swelling * 1  4/268 (1.49%)  10/265 (3.77%) 
Periorbital oedema * 1  4/268 (1.49%)  37/265 (13.96%) 
Vision blurred * 1  4/268 (1.49%)  12/265 (4.53%) 
Eye pain * 1  3/268 (1.12%)  7/265 (2.64%) 
Conjunctival haemorrhage * 1  2/268 (0.75%)  8/265 (3.02%) 
Eye haemorrhage * 1  2/268 (0.75%)  2/265 (0.75%) 
Eye pruritus * 1  2/268 (0.75%)  0/265 (0.00%) 
Ocular hyperaemia * 1  2/268 (0.75%)  3/265 (1.13%) 
Photophobia * 1  2/268 (0.75%)  1/265 (0.38%) 
Retinal haemorrhage * 1  2/268 (0.75%)  0/265 (0.00%) 
Vitreous floaters * 1  2/268 (0.75%)  0/265 (0.00%) 
Cataract * 1  1/268 (0.37%)  2/265 (0.75%) 
Conjunctivitis allergic * 1  1/268 (0.37%)  1/265 (0.38%) 
Eye irritation * 1  1/268 (0.37%)  1/265 (0.38%) 
Eyelid oedema * 1  1/268 (0.37%)  25/265 (9.43%) 
Eyelid ptosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Lacrimal disorder * 1  1/268 (0.37%)  0/265 (0.00%) 
Ocular discomfort * 1  1/268 (0.37%)  0/265 (0.00%) 
Retinal disorder * 1  1/268 (0.37%)  0/265 (0.00%) 
Uveitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Visual acuity reduced * 1  1/268 (0.37%)  2/265 (0.75%) 
Visual impairment * 1  1/268 (0.37%)  2/265 (0.75%) 
Vitreous detachment * 1  1/268 (0.37%)  0/265 (0.00%) 
Conjunctival hyperaemia * 1  0/268 (0.00%)  1/265 (0.38%) 
Diabetic retinopathy * 1  0/268 (0.00%)  1/265 (0.38%) 
Diplopia * 1  0/268 (0.00%)  1/265 (0.38%) 
Dry eye * 1  0/268 (0.00%)  11/265 (4.15%) 
Eye discharge * 1  0/268 (0.00%)  1/265 (0.38%) 
Eye oedema * 1  0/268 (0.00%)  4/265 (1.51%) 
Eyelid pain * 1  0/268 (0.00%)  1/265 (0.38%) 
Glaucoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Hypermetropia * 1  0/268 (0.00%)  1/265 (0.38%) 
Lacrimation increased * 1  0/268 (0.00%)  16/265 (6.04%) 
Ocular toxicity * 1  0/268 (0.00%)  1/265 (0.38%) 
Orbital oedema * 1  0/268 (0.00%)  6/265 (2.26%) 
Retinal detachment * 1  0/268 (0.00%)  1/265 (0.38%) 
Retinopathy haemorrhagic * 1  0/268 (0.00%)  1/265 (0.38%) 
Scleral haemorrhage * 1  0/268 (0.00%)  2/265 (0.75%) 
Gastrointestinal disorders     
Diarrhoea * 1  189/268 (70.52%)  88/265 (33.21%) 
Nausea * 1  94/268 (35.07%)  102/265 (38.49%) 
Vomiting * 1  48/268 (17.91%)  43/265 (16.23%) 
Abdominal pain * 1  47/268 (17.54%)  19/265 (7.17%) 
Constipation * 1  26/268 (9.70%)  14/265 (5.28%) 
Abdominal pain upper * 1  20/268 (7.46%)  19/265 (7.17%) 
Dyspepsia * 1  18/268 (6.72%)  19/265 (7.17%) 
Haemorrhoids * 1  10/268 (3.73%)  4/265 (1.51%) 
Abdominal distension * 1  8/268 (2.99%)  3/265 (1.13%) 
Toothache * 1  6/268 (2.24%)  3/265 (1.13%) 
Flatulence * 1  5/268 (1.87%)  4/265 (1.51%) 
Gastrooesophageal reflux disease * 1  5/268 (1.87%)  8/265 (3.02%) 
Abdominal discomfort * 1  4/268 (1.49%)  6/265 (2.26%) 
Dry mouth * 1  4/268 (1.49%)  7/265 (2.64%) 
Mouth ulceration * 1  4/268 (1.49%)  3/265 (1.13%) 
Haematochezia * 1  3/268 (1.12%)  0/265 (0.00%) 
Epigastric discomfort * 1  2/268 (0.75%)  2/265 (0.75%) 
Gastritis * 1  2/268 (0.75%)  2/265 (0.75%) 
Paraesthesia oral * 1  2/268 (0.75%)  0/265 (0.00%) 
Proctalgia * 1  2/268 (0.75%)  0/265 (0.00%) 
Rectal haemorrhage * 1  2/268 (0.75%)  3/265 (1.13%) 
Abdominal hernia * 1  1/268 (0.37%)  0/265 (0.00%) 
Anal fissure * 1  1/268 (0.37%)  1/265 (0.38%) 
Anal incontinence * 1  1/268 (0.37%)  0/265 (0.00%) 
Aphthous ulcer * 1  1/268 (0.37%)  1/265 (0.38%) 
Colitis * 1  1/268 (0.37%)  1/265 (0.38%) 
Colitis ulcerative * 1  1/268 (0.37%)  0/265 (0.00%) 
Dental caries * 1  1/268 (0.37%)  0/265 (0.00%) 
Dental discomfort * 1  1/268 (0.37%)  0/265 (0.00%) 
Dysphagia * 1  1/268 (0.37%)  0/265 (0.00%) 
Faeces discoloured * 1  1/268 (0.37%)  0/265 (0.00%) 
Food poisoning * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastric disorder * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastric ulcer * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastrointestinal disorder * 1  1/268 (0.37%)  1/265 (0.38%) 
Gastrointestinal necrosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastrointestinal pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Duodenitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Gingival erythema * 1  1/268 (0.37%)  0/265 (0.00%) 
Glossodynia * 1  1/268 (0.37%)  1/265 (0.38%) 
Ileus * 1  1/268 (0.37%)  0/265 (0.00%) 
Lip pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Mouth haemorrhage * 1  1/268 (0.37%)  0/265 (0.00%) 
Oral pain * 1  1/268 (0.37%)  2/265 (0.75%) 
Pancreatitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Peristalsis visible * 1  1/268 (0.37%)  0/265 (0.00%) 
Proctitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Rectal tenesmus * 1  1/268 (0.37%)  0/265 (0.00%) 
Retching * 1  1/268 (0.37%)  0/265 (0.00%) 
Salivary gland enlargement * 1  1/268 (0.37%)  0/265 (0.00%) 
Stomatitis * 1  1/268 (0.37%)  1/265 (0.38%) 
Tongue discolouration * 1  1/268 (0.37%)  0/265 (0.00%) 
Tongue disorder * 1  1/268 (0.37%)  1/265 (0.38%) 
Abdominal pain lower * 1  0/268 (0.00%)  2/265 (0.75%) 
Anal haemorrhage * 1  0/268 (0.00%)  1/265 (0.38%) 
Ascites * 1  0/268 (0.00%)  1/265 (0.38%) 
Chronic gastritis * 1  0/268 (0.00%)  1/265 (0.38%) 
Eructation * 1  0/268 (0.00%)  1/265 (0.38%) 
Faeces soft * 1  0/268 (0.00%)  1/265 (0.38%) 
Frequent bowel movements * 1  0/268 (0.00%)  1/265 (0.38%) 
Gingival bleeding * 1  0/268 (0.00%)  2/265 (0.75%) 
Gingival pain * 1  0/268 (0.00%)  1/265 (0.38%) 
Haematemesis * 1  0/268 (0.00%)  1/265 (0.38%) 
Inguinal hernia * 1  0/268 (0.00%)  2/265 (0.75%) 
Large intestine polyp * 1  0/268 (0.00%)  1/265 (0.38%) 
Lip dry * 1  0/268 (0.00%)  2/265 (0.75%) 
Lip swelling * 1  0/268 (0.00%)  1/265 (0.38%) 
Oesophagitis * 1  0/268 (0.00%)  2/265 (0.75%) 
Salivary hypersecretion * 1  0/268 (0.00%)  1/265 (0.38%) 
Tongue dry * 1  0/268 (0.00%)  1/265 (0.38%) 
Tooth disorder * 1  0/268 (0.00%)  1/265 (0.38%) 
Umbilical hernia * 1  0/268 (0.00%)  1/265 (0.38%) 
General disorders     
Muscle pain/ Joint pain * 1  0/268 (0.00%)  1/265 (0.38%) 
Fatigue * 1  54/268 (20.15%)  47/265 (17.74%) 
Pyrexia * 1  33/268 (12.31%)  21/265 (7.92%) 
Asthenia * 1  32/268 (11.94%)  18/265 (6.79%) 
Oedema peripheral * 1  12/268 (4.48%)  36/265 (13.58%) 
Influenza like illness * 1  10/268 (3.73%)  3/265 (1.13%) 
Non-cardiac chest pain * 1  9/268 (3.36%)  6/265 (2.26%) 
Chills * 1  7/268 (2.61%)  6/265 (2.26%) 
Chest pain * 1  5/268 (1.87%)  6/265 (2.26%) 
Face oedema * 1  5/268 (1.87%)  15/265 (5.66%) 
Pain * 1  4/268 (1.49%)  8/265 (3.02%) 
Feeling hot * 1  3/268 (1.12%)  0/265 (0.00%) 
Malaise * 1  3/268 (1.12%)  4/265 (1.51%) 
Peripheral swelling * 1  3/268 (1.12%)  4/265 (1.51%) 
Chest discomfort * 1  2/268 (0.75%)  3/265 (1.13%) 
Mucosal inflammation * 1  2/268 (0.75%)  1/265 (0.38%) 
Cyst * 1  1/268 (0.37%)  2/265 (0.75%) 
Discomfort * 1  1/268 (0.37%)  2/265 (0.75%) 
Early satiety * 1  1/268 (0.37%)  0/265 (0.00%) 
Granuloma * 1  1/268 (0.37%)  0/265 (0.00%) 
Mucosal dryness * 1  1/268 (0.37%)  0/265 (0.00%) 
Thirst * 1  1/268 (0.37%)  0/265 (0.00%) 
Xerosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Axillary pain * 1  0/268 (0.00%)  1/265 (0.38%) 
Feeling abnormal * 1  0/268 (0.00%)  1/265 (0.38%) 
Feeling cold * 1  0/268 (0.00%)  6/265 (2.26%) 
Impaired healing * 1  0/268 (0.00%)  1/265 (0.38%) 
Local swelling * 1  0/268 (0.00%)  2/265 (0.75%) 
Nodule * 1  0/268 (0.00%)  1/265 (0.38%) 
Polyp * 1  0/268 (0.00%)  1/265 (0.38%) 
Swelling * 1  0/268 (0.00%)  1/265 (0.38%) 
Ulcer * 1  0/268 (0.00%)  1/265 (0.38%) 
Hepatobiliary disorders     
Hepatotoxicity * 1  4/268 (1.49%)  0/265 (0.00%) 
Hyperbilirubinaemia * 1  4/268 (1.49%)  1/265 (0.38%) 
Drug-induced liver injury * 1  1/268 (0.37%)  0/265 (0.00%) 
Hepatitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Hepatitis toxic * 1  1/268 (0.37%)  0/265 (0.00%) 
Hepatocellular injury * 1  1/268 (0.37%)  0/265 (0.00%) 
Jaundice * 1  1/268 (0.37%)  0/265 (0.00%) 
Cholestasis * 1  0/268 (0.00%)  1/265 (0.38%) 
Hepatic steatosis * 1  0/268 (0.00%)  1/265 (0.38%) 
Liver disorder * 1  0/268 (0.00%)  1/265 (0.38%) 
Immune system disorders     
Hypersensitivity * 1  2/268 (0.75%)  2/265 (0.75%) 
Food allergy * 1  1/268 (0.37%)  0/265 (0.00%) 
Rubber sensitivity * 1  1/268 (0.37%)  0/265 (0.00%) 
Seasonal allergy * 1  1/268 (0.37%)  2/265 (0.75%) 
Drug hypersensitivity * 1  0/268 (0.00%)  2/265 (0.75%) 
Infections and infestations     
Nasopharyngitis * 1  26/268 (9.70%)  24/265 (9.06%) 
Upper respiratory tract infection * 1  23/268 (8.58%)  27/265 (10.19%) 
Urinary tract infection * 1  17/268 (6.34%)  9/265 (3.40%) 
Bronchitis * 1  8/268 (2.99%)  4/265 (1.51%) 
Influenza * 1  7/268 (2.61%)  8/265 (3.02%) 
Sinusitis * 1  7/268 (2.61%)  5/265 (1.89%) 
Gastroenteritis * 1  6/268 (2.24%)  5/265 (1.89%) 
Folliculitis * 1  5/268 (1.87%)  2/265 (0.75%) 
Pharyngitis * 1  5/268 (1.87%)  6/265 (2.26%) 
Lower respiratory tract infection * 1  4/268 (1.49%)  1/265 (0.38%) 
Respiratory tract infection * 1  4/268 (1.49%)  2/265 (0.75%) 
Cellulitis * 1  3/268 (1.12%)  0/265 (0.00%) 
Conjunctivitis * 1  3/268 (1.12%)  6/265 (2.26%) 
Otitis media * 1  3/268 (1.12%)  2/265 (0.75%) 
Pneumonia * 1  3/268 (1.12%)  1/265 (0.38%) 
Rhinitis * 1  3/268 (1.12%)  5/265 (1.89%) 
Viral infection * 1  3/268 (1.12%)  7/265 (2.64%) 
Cystitis * 1  2/268 (0.75%)  1/265 (0.38%) 
Ear infection * 1  2/268 (0.75%)  1/265 (0.38%) 
Eye infection * 1  2/268 (0.75%)  2/265 (0.75%) 
Gastroenteritis viral * 1  2/268 (0.75%)  2/265 (0.75%) 
Oral herpes * 1  2/268 (0.75%)  2/265 (0.75%) 
Candida infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Chlamydial infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Ear lobe infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Erysipelas * 1  1/268 (0.37%)  0/265 (0.00%) 
Gastrointestinal infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Hepatitis B * 1  1/268 (0.37%)  0/265 (0.00%) 
Herpes zoster * 1  1/268 (0.37%)  3/265 (1.13%) 
Infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Lice infestation * 1  1/268 (0.37%)  0/265 (0.00%) 
Lip infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Lymphadenitis bacterial * 1  1/268 (0.37%)  0/265 (0.00%) 
Oral candidiasis * 1  1/268 (0.37%)  2/265 (0.75%) 
Paronychia * 1  1/268 (0.37%)  1/265 (0.38%) 
Pulpitis dental * 1  1/268 (0.37%)  2/265 (0.75%) 
Respiratory tract infection viral * 1  1/268 (0.37%)  2/265 (0.75%) 
Skin infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Staphylococcal infection * 1  1/268 (0.37%)  0/265 (0.00%) 
Tooth abscess * 1  1/268 (0.37%)  2/265 (0.75%) 
Tooth infection * 1  1/268 (0.37%)  1/265 (0.38%) 
Adenovirus infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Carbuncle * 1  0/268 (0.00%)  1/265 (0.38%) 
Diarrhoea infectious * 1  0/268 (0.00%)  1/265 (0.38%) 
Enterocolitis infectious * 1  0/268 (0.00%)  1/265 (0.38%) 
Escherichia urinary tract infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Fungal skin infection * 1  0/268 (0.00%)  3/265 (1.13%) 
Genital abscess * 1  0/268 (0.00%)  1/265 (0.38%) 
Gingivitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Helicobacter infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Herpes simplex * 1  0/268 (0.00%)  1/265 (0.38%) 
Hordeolum * 1  0/268 (0.00%)  1/265 (0.38%) 
Labyrinthitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Localised infection * 1  0/268 (0.00%)  4/265 (1.51%) 
Lung infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Meningococcal infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Nail infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Onychomycosis * 1  0/268 (0.00%)  1/265 (0.38%) 
Parainfluenzae virus infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Pharyngitis streptococcal * 1  0/268 (0.00%)  2/265 (0.75%) 
Pneumonia bacterial * 1  0/268 (0.00%)  1/265 (0.38%) 
Pyelonephritis chronic * 1  0/268 (0.00%)  1/265 (0.38%) 
Tonsillitis bacterial * 1  0/268 (0.00%)  1/265 (0.38%) 
Vaginal infection * 1  0/268 (0.00%)  1/265 (0.38%) 
Injury, poisoning and procedural complications     
Contusion * 1  7/268 (2.61%)  3/265 (1.13%) 
Fall * 1  4/268 (1.49%)  0/265 (0.00%) 
Arthropod bite * 1  1/268 (0.37%)  0/265 (0.00%) 
Hand fracture * 1  1/268 (0.37%)  0/265 (0.00%) 
Heavy exposure to ultraviolet light * 1  1/268 (0.37%)  0/265 (0.00%) 
Laceration * 1  1/268 (0.37%)  1/265 (0.38%) 
Ligament sprain * 1  1/268 (0.37%)  0/265 (0.00%) 
Limb injury * 1  1/268 (0.37%)  0/265 (0.00%) 
Lip injury * 1  1/268 (0.37%)  0/265 (0.00%) 
Nerve injury * 1  1/268 (0.37%)  0/265 (0.00%) 
Post procedural haematoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Procedural pain * 1  1/268 (0.37%)  3/265 (1.13%) 
Radius fracture * 1  1/268 (0.37%)  0/265 (0.00%) 
Rib fracture * 1  1/268 (0.37%)  0/265 (0.00%) 
Spinal fracture * 1  1/268 (0.37%)  0/265 (0.00%) 
Sunburn * 1  1/268 (0.37%)  2/265 (0.75%) 
Tooth fracture * 1  1/268 (0.37%)  0/265 (0.00%) 
Wound dehiscence * 1  1/268 (0.37%)  0/265 (0.00%) 
Animal bite * 1  0/268 (0.00%)  1/265 (0.38%) 
Eye injury * 1  0/268 (0.00%)  1/265 (0.38%) 
Gun shot wound * 1  0/268 (0.00%)  1/265 (0.38%) 
Keratorhexis * 1  0/268 (0.00%)  1/265 (0.38%) 
Muscle rupture * 1  0/268 (0.00%)  1/265 (0.38%) 
Muscle strain * 1  0/268 (0.00%)  3/265 (1.13%) 
Poisoning * 1  0/268 (0.00%)  1/265 (0.38%) 
Skin abrasion * 1  0/268 (0.00%)  1/265 (0.38%) 
Wound * 1  0/268 (0.00%)  1/265 (0.38%) 
Ankle fracture * 1  1/268 (0.37%)  0/265 (0.00%) 
Foot fracture * 1  1/268 (0.37%)  0/265 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  81/268 (30.22%)  15/265 (5.66%) 
Aspartate aminotransferase increased * 1  60/268 (22.39%)  17/265 (6.42%) 
Lipase increased * 1  36/268 (13.43%)  22/265 (8.30%) 
Platelet count decreased * 1  33/268 (12.31%)  20/265 (7.55%) 
Blood alkaline phosphatase increased * 1  15/268 (5.60%)  9/265 (3.40%) 
Blood creatinine increased * 1  15/268 (5.60%)  17/265 (6.42%) 
Amylase increased * 1  14/268 (5.22%)  7/265 (2.64%) 
Blood bilirubin increased * 1  13/268 (4.85%)  6/265 (2.26%) 
Blood creatine phosphokinase increased * 1  9/268 (3.36%)  19/265 (7.17%) 
Weight decreased * 1  8/268 (2.99%)  5/265 (1.89%) 
Weight increased * 1  8/268 (2.99%)  13/265 (4.91%) 
Blood uric acid increased * 1  7/268 (2.61%)  2/265 (0.75%) 
Transaminases increased * 1  7/268 (2.61%)  2/265 (0.75%) 
Blood cholesterol increased * 1  6/268 (2.24%)  1/265 (0.38%) 
Gamma-glutamyltransferase increased * 1  6/268 (2.24%)  4/265 (1.51%) 
White blood cell count decreased * 1  6/268 (2.24%)  14/265 (5.28%) 
Electrocardiogram QT prolonged * 1  4/268 (1.49%)  8/265 (3.02%) 
Hepatic enzyme increased * 1  4/268 (1.49%)  0/265 (0.00%) 
Neutrophil count decreased * 1  4/268 (1.49%)  11/265 (4.15%) 
Blood urea increased * 1  3/268 (1.12%)  2/265 (0.75%) 
Haemoglobin decreased * 1  3/268 (1.12%)  4/265 (1.51%) 
Lymphocyte count decreased * 1  3/268 (1.12%)  4/265 (1.51%) 
Blood glucose increased * 1  2/268 (0.75%)  3/265 (1.13%) 
Blood lactate dehydrogenase increased * 1  2/268 (0.75%)  1/265 (0.38%) 
Liver function test increased * 1  2/268 (0.75%)  1/265 (0.38%) 
White blood cell count increased * 1  2/268 (0.75%)  0/265 (0.00%) 
Activated partial thromboplastin time prolonged * 1  1/268 (0.37%)  1/265 (0.38%) 
Aspartate aminotransferase * 1  1/268 (0.37%)  0/265 (0.00%) 
Blood bicarbonate decreased * 1  1/268 (0.37%)  0/265 (0.00%) 
Blood chloride increased * 1  1/268 (0.37%)  0/265 (0.00%) 
Blood iron decreased * 1  1/268 (0.37%)  0/265 (0.00%) 
Blood phosphorus decreased * 1  1/268 (0.37%)  3/265 (1.13%) 
Blood urine present * 1  1/268 (0.37%)  0/265 (0.00%) 
C-reactive protein increased * 1  1/268 (0.37%)  2/265 (0.75%) 
Cardiac murmur * 1  1/268 (0.37%)  1/265 (0.38%) 
Electrocardiogram QT interval * 1  1/268 (0.37%)  0/265 (0.00%) 
Electrocardiogram ST-T segment abnormal * 1  1/268 (0.37%)  0/265 (0.00%) 
Electrocardiogram T wave amplitude decreased * 1  1/268 (0.37%)  0/265 (0.00%) 
Eosinophil count decreased * 1  1/268 (0.37%)  0/265 (0.00%) 
Occult blood positive * 1  1/268 (0.37%)  0/265 (0.00%) 
Platelet count increased * 1  1/268 (0.37%)  1/265 (0.38%) 
Protein urine * 1  1/268 (0.37%)  0/265 (0.00%) 
Serum ferritin decreased * 1  1/268 (0.37%)  1/265 (0.38%) 
Basophil count increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Blood creatine phosphokinase MB increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Blood folate decreased * 1  0/268 (0.00%)  1/265 (0.38%) 
Blood magnesium decreased * 1  0/268 (0.00%)  1/265 (0.38%) 
Blood potassium decreased * 1  0/268 (0.00%)  2/265 (0.75%) 
Blood pressure systolic increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Blood triglycerides increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Body temperature increased * 1  0/268 (0.00%)  2/265 (0.75%) 
Eosinophil count increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Globulins decreased * 1  0/268 (0.00%)  1/265 (0.38%) 
Heart rate increased * 1  0/268 (0.00%)  4/265 (1.51%) 
Heart rate irregular * 1  0/268 (0.00%)  1/265 (0.38%) 
International normalised ratio increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Lipids abnormal * 1  0/268 (0.00%)  1/265 (0.38%) 
Lymph node palpable * 1  0/268 (0.00%)  1/265 (0.38%) 
Lymphocyte count increased * 1  0/268 (0.00%)  2/265 (0.75%) 
Neutrophil count increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Nicotinamide decreased * 1  0/268 (0.00%)  1/265 (0.38%) 
Prostatic specific antigen increased * 1  0/268 (0.00%)  2/265 (0.75%) 
Protein total decreased * 1  0/268 (0.00%)  1/265 (0.38%) 
Prothrombin time prolonged * 1  0/268 (0.00%)  1/265 (0.38%) 
Pulmonary arterial pressure increased * 1  0/268 (0.00%)  1/265 (0.38%) 
Urinary sediment present * 1  0/268 (0.00%)  1/265 (0.38%) 
Bilirubin conjugated increased * 1  2/268 (0.75%)  0/265 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  26/268 (9.70%)  16/265 (6.04%) 
Hyperuricaemia * 1  5/268 (1.87%)  4/265 (1.51%) 
Hypophosphataemia * 1  5/268 (1.87%)  14/265 (5.28%) 
Gout * 1  4/268 (1.49%)  2/265 (0.75%) 
Hyperglycaemia * 1  4/268 (1.49%)  8/265 (3.02%) 
Hyperkalaemia * 1  4/268 (1.49%)  4/265 (1.51%) 
Hypertriglyceridaemia * 1  4/268 (1.49%)  2/265 (0.75%) 
Hypokalaemia * 1  4/268 (1.49%)  18/265 (6.79%) 
Hypercholesterolaemia * 1  3/268 (1.12%)  0/265 (0.00%) 
Hypocalcaemia * 1  3/268 (1.12%)  8/265 (3.02%) 
Hypomagnesaemia * 1  3/268 (1.12%)  2/265 (0.75%) 
Vitamin D deficiency * 1  3/268 (1.12%)  0/265 (0.00%) 
Dehydration * 1  2/268 (0.75%)  2/265 (0.75%) 
Hyperchloraemia * 1  2/268 (0.75%)  0/265 (0.00%) 
Hyponatraemia * 1  2/268 (0.75%)  2/265 (0.75%) 
Diabetes mellitus * 1  1/268 (0.37%)  0/265 (0.00%) 
Folate deficiency * 1  1/268 (0.37%)  0/265 (0.00%) 
Hypoalbuminaemia * 1  1/268 (0.37%)  4/265 (1.51%) 
Hypoglycaemia * 1  1/268 (0.37%)  5/265 (1.89%) 
Iron deficiency * 1  1/268 (0.37%)  1/265 (0.38%) 
Obesity * 1  1/268 (0.37%)  0/265 (0.00%) 
Vitamin B12 deficiency * 1  1/268 (0.37%)  1/265 (0.38%) 
Electrolyte imbalance * 1  0/268 (0.00%)  1/265 (0.38%) 
Fluid retention * 1  0/268 (0.00%)  8/265 (3.02%) 
Hypermagnesaemia * 1  0/268 (0.00%)  1/265 (0.38%) 
Increased appetite * 1  0/268 (0.00%)  1/265 (0.38%) 
Metabolic syndrome * 1  0/268 (0.00%)  1/265 (0.38%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  32/268 (11.94%)  35/265 (13.21%) 
Back pain * 1  22/268 (8.21%)  19/265 (7.17%) 
Pain in extremity * 1  12/268 (4.48%)  34/265 (12.83%) 
Myalgia * 1  8/268 (2.99%)  41/265 (15.47%) 
Bone pain * 1  7/268 (2.61%)  18/265 (6.79%) 
Musculoskeletal pain * 1  7/268 (2.61%)  8/265 (3.02%) 
Muscle spasms * 1  6/268 (2.24%)  70/265 (26.42%) 
Neck pain * 1  6/268 (2.24%)  4/265 (1.51%) 
Musculoskeletal chest pain * 1  4/268 (1.49%)  0/265 (0.00%) 
Flank pain * 1  3/268 (1.12%)  2/265 (0.75%) 
Muscular weakness * 1  2/268 (0.75%)  1/265 (0.38%) 
Osteoarthritis * 1  2/268 (0.75%)  3/265 (1.13%) 
Spinal pain * 1  2/268 (0.75%)  1/265 (0.38%) 
Synovial cyst * 1  2/268 (0.75%)  1/265 (0.38%) 
Intervertebral disc disorder * 1  1/268 (0.37%)  0/265 (0.00%) 
Joint effusion * 1  1/268 (0.37%)  1/265 (0.38%) 
Joint instability * 1  1/268 (0.37%)  0/265 (0.00%) 
Limb discomfort * 1  1/268 (0.37%)  0/265 (0.00%) 
Muscle fatigue * 1  1/268 (0.37%)  0/265 (0.00%) 
Musculoskeletal discomfort * 1  1/268 (0.37%)  0/265 (0.00%) 
Myopathy * 1  1/268 (0.37%)  0/265 (0.00%) 
Osteoporosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Rheumatoid arthritis * 1  1/268 (0.37%)  0/265 (0.00%) 
Spinal column stenosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Spinal osteoarthritis * 1  1/268 (0.37%)  0/265 (0.00%) 
Arthritis * 1  0/268 (0.00%)  2/265 (0.75%) 
Dupuytren's contracture * 1  0/268 (0.00%)  1/265 (0.38%) 
Foot deformity * 1  0/268 (0.00%)  1/265 (0.38%) 
Growing pains * 1  0/268 (0.00%)  1/265 (0.38%) 
Intervertebral disc protrusion * 1  0/268 (0.00%)  1/265 (0.38%) 
Joint laxity * 1  0/268 (0.00%)  1/265 (0.38%) 
Joint stiffness * 1  0/268 (0.00%)  1/265 (0.38%) 
Muscle contracture * 1  0/268 (0.00%)  1/265 (0.38%) 
Muscle twitching * 1  0/268 (0.00%)  1/265 (0.38%) 
Musculoskeletal stiffness * 1  0/268 (0.00%)  2/265 (0.75%) 
Osteochondrosis * 1  0/268 (0.00%)  1/265 (0.38%) 
Pain in jaw * 1  0/268 (0.00%)  1/265 (0.38%) 
Rhabdomyolysis * 1  0/268 (0.00%)  1/265 (0.38%) 
Temporomandibular joint syndrome * 1  0/268 (0.00%)  1/265 (0.38%) 
Tenosynovitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Torticollis * 1  0/268 (0.00%)  1/265 (0.38%) 
Trismus * 1  0/268 (0.00%)  1/265 (0.38%) 
Tendonitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma * 1  3/268 (1.12%)  0/265 (0.00%) 
Acanthoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Adrenal adenoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Prostatic adenoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Seborrhoeic keratosis * 1  0/268 (0.00%)  1/265 (0.38%) 
Skin cancer * 1  0/268 (0.00%)  1/265 (0.38%) 
Anogenital warts * 1  1/268 (0.37%)  0/265 (0.00%) 
Leukaemic retinopathy * 1  1/268 (0.37%)  0/265 (0.00%) 
Skin papilloma * 1  1/268 (0.37%)  1/265 (0.38%) 
Lipoma * 1  0/268 (0.00%)  1/265 (0.38%) 
Melanocytic naevus * 1  0/268 (0.00%)  1/265 (0.38%) 
Nervous system disorders     
Headache * 1  49/268 (18.28%)  35/265 (13.21%) 
Dizziness * 1  19/268 (7.09%)  19/265 (7.17%) 
Paraesthesia * 1  6/268 (2.24%)  2/265 (0.75%) 
Lethargy * 1  5/268 (1.87%)  6/265 (2.26%) 
Memory impairment * 1  5/268 (1.87%)  2/265 (0.75%) 
Disturbance in attention * 1  4/268 (1.49%)  1/265 (0.38%) 
Dysgeusia * 1  4/268 (1.49%)  9/265 (3.40%) 
Hypoaesthesia * 1  4/268 (1.49%)  2/265 (0.75%) 
Peripheral sensory neuropathy * 1  4/268 (1.49%)  1/265 (0.38%) 
Dysaesthesia * 1  2/268 (0.75%)  0/265 (0.00%) 
Amnesia * 1  1/268 (0.37%)  2/265 (0.75%) 
Ataxia * 1  1/268 (0.37%)  0/265 (0.00%) 
Burning sensation * 1  1/268 (0.37%)  0/265 (0.00%) 
Dizziness postural * 1  1/268 (0.37%)  0/265 (0.00%) 
Migraine * 1  1/268 (0.37%)  0/265 (0.00%) 
Muscle contractions involuntary * 1  1/268 (0.37%)  1/265 (0.38%) 
Nerve compression * 1  1/268 (0.37%)  0/265 (0.00%) 
Neuralgia * 1  1/268 (0.37%)  0/265 (0.00%) 
Neuropathy peripheral * 1  1/268 (0.37%)  3/265 (1.13%) 
Peripheral motor neuropathy * 1  1/268 (0.37%)  2/265 (0.75%) 
Presyncope * 1  1/268 (0.37%)  0/265 (0.00%) 
Sciatica * 1  1/268 (0.37%)  4/265 (1.51%) 
Somnolence * 1  1/268 (0.37%)  6/265 (2.26%) 
Syncope * 1  1/268 (0.37%)  4/265 (1.51%) 
Tremor * 1  1/268 (0.37%)  2/265 (0.75%) 
Ageusia * 1  0/268 (0.00%)  1/265 (0.38%) 
Balance disorder * 1  0/268 (0.00%)  1/265 (0.38%) 
Intercostal neuralgia * 1  0/268 (0.00%)  1/265 (0.38%) 
Migraine with aura * 1  0/268 (0.00%)  1/265 (0.38%) 
Restless legs syndrome * 1  0/268 (0.00%)  1/265 (0.38%) 
Psychiatric disorders     
Insomnia * 1  15/268 (5.60%)  16/265 (6.04%) 
Anxiety * 1  10/268 (3.73%)  10/265 (3.77%) 
Depression * 1  8/268 (2.99%)  10/265 (3.77%) 
Libido decreased * 1  2/268 (0.75%)  0/265 (0.00%) 
Confusional state * 1  1/268 (0.37%)  1/265 (0.38%) 
Delirium * 1  1/268 (0.37%)  0/265 (0.00%) 
Depressive symptom * 1  1/268 (0.37%)  0/265 (0.00%) 
Mood altered * 1  1/268 (0.37%)  0/265 (0.00%) 
Sleep disorder * 1  1/268 (0.37%)  1/265 (0.38%) 
Irritability * 1  0/268 (0.00%)  1/265 (0.38%) 
Mood swings * 1  0/268 (0.00%)  2/265 (0.75%) 
Nightmare * 1  0/268 (0.00%)  1/265 (0.38%) 
Renal and urinary disorders     
Nocturia * 1  3/268 (1.12%)  1/265 (0.38%) 
Acute kidney injury * 1  2/268 (0.75%)  1/265 (0.38%) 
Dysuria * 1  2/268 (0.75%)  0/265 (0.00%) 
Haematuria * 1  2/268 (0.75%)  6/265 (2.26%) 
Pollakiuria * 1  2/268 (0.75%)  3/265 (1.13%) 
Renal impairment * 1  2/268 (0.75%)  0/265 (0.00%) 
Urethritis noninfective * 1  2/268 (0.75%)  0/265 (0.00%) 
Bladder diverticulum * 1  1/268 (0.37%)  0/265 (0.00%) 
Calculus urinary * 1  1/268 (0.37%)  0/265 (0.00%) 
Chromaturia * 1  1/268 (0.37%)  1/265 (0.38%) 
Nephritis * 1  1/268 (0.37%)  0/265 (0.00%) 
Nephrocalcinosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Nephroptosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Oliguria * 1  1/268 (0.37%)  0/265 (0.00%) 
Polyuria * 1  1/268 (0.37%)  0/265 (0.00%) 
Proteinuria * 1  1/268 (0.37%)  3/265 (1.13%) 
Renal cyst * 1  1/268 (0.37%)  1/265 (0.38%) 
Urinary tract pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Urine abnormality * 1  1/268 (0.37%)  1/265 (0.38%) 
Acute prerenal failure * 1  0/268 (0.00%)  1/265 (0.38%) 
Calculus urethral * 1  0/268 (0.00%)  1/265 (0.38%) 
Nephropathy * 1  0/268 (0.00%)  1/265 (0.38%) 
Nephrotic syndrome * 1  0/268 (0.00%)  1/265 (0.38%) 
Renal injury * 1  0/268 (0.00%)  1/265 (0.38%) 
Urinary retention * 1  0/268 (0.00%)  2/265 (0.75%) 
Urinary tract inflammation * 1  0/268 (0.00%)  1/265 (0.38%) 
Reproductive system and breast disorders     
Amenorrhoea * 1  2/268 (0.75%)  2/265 (0.75%) 
Benign prostatic hyperplasia * 1  2/268 (0.75%)  2/265 (0.75%) 
Dysmenorrhoea * 1  2/268 (0.75%)  0/265 (0.00%) 
Menstruation irregular * 1  2/268 (0.75%)  0/265 (0.00%) 
Adnexa uteri cyst * 1  1/268 (0.37%)  0/265 (0.00%) 
Breast haematoma * 1  1/268 (0.37%)  0/265 (0.00%) 
Endometriosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Menopausal symptoms * 1  1/268 (0.37%)  0/265 (0.00%) 
Menorrhagia * 1  1/268 (0.37%)  3/265 (1.13%) 
Prostatitis * 1  1/268 (0.37%)  1/265 (0.38%) 
Prostatomegaly * 1  1/268 (0.37%)  0/265 (0.00%) 
Testicular mass * 1  1/268 (0.37%)  0/265 (0.00%) 
Erectile dysfunction * 1  0/268 (0.00%)  1/265 (0.38%) 
Genital haemorrhage * 1  0/268 (0.00%)  1/265 (0.38%) 
Menstruation delayed * 1  0/268 (0.00%)  1/265 (0.38%) 
Pelvic pain * 1  0/268 (0.00%)  4/265 (1.51%) 
Prostatic dysplasia * 1  0/268 (0.00%)  1/265 (0.38%) 
Sexual dysfunction * 1  0/268 (0.00%)  1/265 (0.38%) 
Vaginal haemorrhage * 1  0/268 (0.00%)  3/265 (1.13%) 
Vulvovaginal pruritus * 1  0/268 (0.00%)  1/265 (0.38%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  22/268 (8.21%)  10/265 (3.77%) 
Cough * 1  21/268 (7.84%)  18/265 (6.79%) 
Oropharyngeal pain * 1  13/268 (4.85%)  9/265 (3.40%) 
Epistaxis * 1  10/268 (3.73%)  7/265 (2.64%) 
Pleural effusion * 1  4/268 (1.49%)  3/265 (1.13%) 
Productive cough * 1  4/268 (1.49%)  3/265 (1.13%) 
Rhinorrhoea * 1  3/268 (1.12%)  2/265 (0.75%) 
Asthma * 1  2/268 (0.75%)  1/265 (0.38%) 
Catarrh * 1  1/268 (0.37%)  0/265 (0.00%) 
Chronic obstructive pulmonary disease * 1  1/268 (0.37%)  0/265 (0.00%) 
Dysphonia * 1  1/268 (0.37%)  4/265 (1.51%) 
Emphysema * 1  1/268 (0.37%)  1/265 (0.38%) 
Haemoptysis * 1  1/268 (0.37%)  1/265 (0.38%) 
Lung infiltration * 1  1/268 (0.37%)  0/265 (0.00%) 
Nasal congestion * 1  1/268 (0.37%)  2/265 (0.75%) 
Pleuritic pain * 1  1/268 (0.37%)  0/265 (0.00%) 
Respiratory tract congestion * 1  1/268 (0.37%)  0/265 (0.00%) 
Rhinitis allergic * 1  1/268 (0.37%)  3/265 (1.13%) 
Sinus congestion * 1  1/268 (0.37%)  1/265 (0.38%) 
Throat irritation * 1  1/268 (0.37%)  1/265 (0.38%) 
Throat tightness * 1  1/268 (0.37%)  1/265 (0.38%) 
Tonsillar hypertrophy * 1  1/268 (0.37%)  0/265 (0.00%) 
Wheezing * 1  1/268 (0.37%)  0/265 (0.00%) 
Dry throat * 1  0/268 (0.00%)  1/265 (0.38%) 
Dyspnoea exertional * 1  0/268 (0.00%)  2/265 (0.75%) 
Hypoxia * 1  0/268 (0.00%)  3/265 (1.13%) 
Laryngeal inflammation * 1  0/268 (0.00%)  1/265 (0.38%) 
Nasal ulcer * 1  0/268 (0.00%)  1/265 (0.38%) 
Rales * 1  0/268 (0.00%)  1/265 (0.38%) 
Respiratory failure * 1  0/268 (0.00%)  1/265 (0.38%) 
Sneezing * 1  0/268 (0.00%)  1/265 (0.38%) 
Upper-airway cough syndrome * 1  0/268 (0.00%)  1/265 (0.38%) 
Skin and subcutaneous tissue disorders     
Rash * 1  53/268 (19.78%)  36/265 (13.58%) 
Pruritus * 1  25/268 (9.33%)  7/265 (2.64%) 
Rash maculo-papular * 1  14/268 (5.22%)  14/265 (5.28%) 
Alopecia * 1  12/268 (4.48%)  12/265 (4.53%) 
Dry skin * 1  12/268 (4.48%)  10/265 (3.77%) 
Erythema * 1  9/268 (3.36%)  4/265 (1.51%) 
Rash pruritic * 1  7/268 (2.61%)  0/265 (0.00%) 
Acne * 1  6/268 (2.24%)  1/265 (0.38%) 
Dermatitis acneiform * 1  5/268 (1.87%)  1/265 (0.38%) 
Urticaria * 1  5/268 (1.87%)  3/265 (1.13%) 
Eczema * 1  4/268 (1.49%)  6/265 (2.26%) 
Hyperhidrosis * 1  4/268 (1.49%)  6/265 (2.26%) 
Rash papular * 1  4/268 (1.49%)  0/265 (0.00%) 
Dermatitis * 1  3/268 (1.12%)  1/265 (0.38%) 
Nail discolouration * 1  3/268 (1.12%)  1/265 (0.38%) 
Rash erythematous * 1  3/268 (1.12%)  2/265 (0.75%) 
Skin lesion * 1  3/268 (1.12%)  1/265 (0.38%) 
Actinic keratosis * 1  2/268 (0.75%)  1/265 (0.38%) 
Dermatitis allergic * 1  2/268 (0.75%)  4/265 (1.51%) 
Dyshidrotic eczema * 1  2/268 (0.75%)  0/265 (0.00%) 
Miliaria * 1  2/268 (0.75%)  1/265 (0.38%) 
Pruritus generalised * 1  2/268 (0.75%)  1/265 (0.38%) 
Skin discolouration * 1  2/268 (0.75%)  1/265 (0.38%) 
Skin exfoliation * 1  2/268 (0.75%)  1/265 (0.38%) 
Angioedema * 1  1/268 (0.37%)  0/265 (0.00%) 
Blister * 1  1/268 (0.37%)  1/265 (0.38%) 
Dermal cyst * 1  1/268 (0.37%)  0/265 (0.00%) 
Dermatitis exfoliative * 1  1/268 (0.37%)  0/265 (0.00%) 
Drug reaction with eosinophilia and systemic symptoms * 1  1/268 (0.37%)  0/265 (0.00%) 
Ecchymosis * 1  1/268 (0.37%)  2/265 (0.75%) 
Generalised erythema * 1  1/268 (0.37%)  1/265 (0.38%) 
Hyperkeratosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Hypertrichosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Ingrowing nail * 1  1/268 (0.37%)  1/265 (0.38%) 
Mucocutaneous ulceration * 1  1/268 (0.37%)  0/265 (0.00%) 
Nail disorder * 1  1/268 (0.37%)  0/265 (0.00%) 
Nail dystrophy * 1  1/268 (0.37%)  0/265 (0.00%) 
Perivascular dermatitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Photosensitivity reaction * 1  1/268 (0.37%)  0/265 (0.00%) 
Purpura * 1  1/268 (0.37%)  0/265 (0.00%) 
Rash generalised * 1  1/268 (0.37%)  0/265 (0.00%) 
Sebaceous glands overactivity * 1  1/268 (0.37%)  0/265 (0.00%) 
Skin fragility * 1  1/268 (0.37%)  1/265 (0.38%) 
Skin mass * 1  1/268 (0.37%)  0/265 (0.00%) 
Skin ulcer * 1  1/268 (0.37%)  0/265 (0.00%) 
Swelling face * 1  1/268 (0.37%)  0/265 (0.00%) 
Vitiligo * 1  1/268 (0.37%)  0/265 (0.00%) 
Dandruff * 1  0/268 (0.00%)  1/265 (0.38%) 
Diffuse alopecia * 1  0/268 (0.00%)  1/265 (0.38%) 
Eczema asteatotic * 1  0/268 (0.00%)  1/265 (0.38%) 
Erythema multiforme * 1  0/268 (0.00%)  2/265 (0.75%) 
Erythema nodosum * 1  0/268 (0.00%)  1/265 (0.38%) 
Petechiae * 1  0/268 (0.00%)  1/265 (0.38%) 
Psoriasis * 1  0/268 (0.00%)  1/265 (0.38%) 
Rash macular * 1  0/268 (0.00%)  2/265 (0.75%) 
Skin hypopigmentation * 1  0/268 (0.00%)  1/265 (0.38%) 
Stasis dermatitis * 1  0/268 (0.00%)  1/265 (0.38%) 
Toxic skin eruption * 1  0/268 (0.00%)  1/265 (0.38%) 
Papule * 1  1/268 (0.37%)  0/265 (0.00%) 
Night sweats * 1  5/268 (1.87%)  9/265 (3.40%) 
Surgical and medical procedures     
Cholecystectomy * 1  1/268 (0.37%)  0/265 (0.00%) 
Debridement * 1  1/268 (0.37%)  0/265 (0.00%) 
Hernia hiatus repair * 1  1/268 (0.37%)  0/265 (0.00%) 
Hip arthroplasty * 1  1/268 (0.37%)  0/265 (0.00%) 
Inguinal hernia repair * 1  1/268 (0.37%)  0/265 (0.00%) 
Medical induction of coma * 1  1/268 (0.37%)  0/265 (0.00%) 
Tooth extraction * 1  1/268 (0.37%)  0/265 (0.00%) 
Transfusion * 1  1/268 (0.37%)  0/265 (0.00%) 
Cyst drainage * 1  0/268 (0.00%)  1/265 (0.38%) 
Endodontic procedure * 1  0/268 (0.00%)  1/265 (0.38%) 
Vitrectomy * 1  0/268 (0.00%)  1/265 (0.38%) 
Vascular disorders     
Hypertension * 1  13/268 (4.85%)  16/265 (6.04%) 
Haematoma * 1  5/268 (1.87%)  3/265 (1.13%) 
Hypotension * 1  5/268 (1.87%)  5/265 (1.89%) 
Angiopathy * 1  1/268 (0.37%)  0/265 (0.00%) 
Capillary fragility * 1  1/268 (0.37%)  0/265 (0.00%) 
Deep vein thrombosis * 1  1/268 (0.37%)  0/265 (0.00%) 
Flushing * 1  1/268 (0.37%)  0/265 (0.00%) 
Hot flush * 1  1/268 (0.37%)  1/265 (0.38%) 
Jugular vein distension * 1  1/268 (0.37%)  0/265 (0.00%) 
Orthostatic hypotension * 1  1/268 (0.37%)  1/265 (0.38%) 
Pallor * 1  1/268 (0.37%)  1/265 (0.38%) 
Periphlebitis * 1  1/268 (0.37%)  0/265 (0.00%) 
Phlebitis * 1  1/268 (0.37%)  2/265 (0.75%) 
Venous thrombosis limb * 1  1/268 (0.37%)  0/265 (0.00%) 
Iliac artery occlusion * 1  0/268 (0.00%)  1/265 (0.38%) 
Peripheral coldness * 1  0/268 (0.00%)  2/265 (0.75%) 
1
Term from vocabulary, MedDRA v19.0
*
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
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02130557     History of Changes
Other Study ID Numbers: AV001
2013-005101-31 ( EudraCT Number )
B1871053 ( Other Identifier: Alias Study Number )
First Submitted: May 1, 2014
First Posted: May 5, 2014
Results First Submitted: July 13, 2018
Results First Posted: November 14, 2018
Last Update Posted: December 10, 2018