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SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction

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ClinicalTrials.gov Identifier: NCT02348489
Recruitment Status : Completed
First Posted : January 28, 2015
Results First Posted : January 14, 2021
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Myeloid, Acute
Interventions Drug: SGI-110 (guadecitabine)
Drug: Treatment Choice
Enrollment 815
Recruitment Details A total of 949 participants were assessed for inclusion in the study. Of these, 134 participants failed screening assessments and 815 participants were randomized.
Pre-assignment Details For the efficacy analysis (all randomized participants), the total duration was 38 months, with a median follow-up of 766 days (25.5 months), lower quartile follow-up of 671 days (22.4 months), and upper quartile follow-up of 896 days (29.9 months). For safety analysis (all treated participants), total duration was 51 months. Combining participants into a single group as part of the Treatment Choice arm was pre-specified as part of the study design.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles. One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Period Title: Overall Study
Started 408 407
Completed 55 40
Not Completed 353 367
Reason Not Completed
Death             336             335
Withdrawal by Subject             14             27
Lost to Follow-up             3             5
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice Total
Hide Arm/Group Description Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles. One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days. Total of all reporting groups
Overall Number of Baseline Participants 408 407 815
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 408 participants 407 participants 815 participants
75.9  (6.2) 75.9  (5.8) 75.9  (6.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 408 participants 407 participants 815 participants
Female
177
  43.4%
165
  40.5%
342
  42.0%
Male
231
  56.6%
242
  59.5%
473
  58.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 408 participants 407 participants 815 participants
Hispanic or Latino
15
   3.7%
14
   3.4%
29
   3.6%
Not Hispanic or Latino
365
  89.5%
345
  84.8%
710
  87.1%
Unknown or Not Reported
28
   6.9%
48
  11.8%
76
   9.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 408 participants 407 participants 815 participants
American Indian or Alaska Native
0
   0.0%
1
   0.2%
1
   0.1%
Asian
71
  17.4%
74
  18.2%
145
  17.8%
Native Hawaiian or Other Pacific Islander
2
   0.5%
0
   0.0%
2
   0.2%
Black or African American
9
   2.2%
5
   1.2%
14
   1.7%
White
311
  76.2%
291
  71.5%
602
  73.9%
More than one race
0
   0.0%
1
   0.2%
1
   0.1%
Unknown or Not Reported
15
   3.7%
35
   8.6%
50
   6.1%
1.Primary Outcome
Title Number of Participants With a Complete Response (CR)
Hide Description Number of participants with a best response of CR assessed based on International Working Group 2003 acute myeloid leukemia (AML) response criteria by a blinded independent pathologist.
Time Frame Up to 38 months (median follow-up of 25.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 408 407
Measure Type: Count of Participants
Unit of Measure: Participants
79
  19.4%
71
  17.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SGI-110 (Guadecitabine), Treatment Choice
Comments The complete response rate was compared between the treatment groups using a Cochran Mantel-Haenszel (CMH) test at an alpha level of 0.04 stratified to adjust for stratification factors used at randomization: age (<75 or >=75), Eastern Cooperative Oncology Group (ECOG) performance status (0-1, 2-3), study center region (North American, Europe, Rest of World), and secondary AML (secondary to MDS or other antecedent hematologic disorder) or poor-risk cytogenetics (Yes, No/Unknown).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rate (%)
Estimated Value 1.92
Confidence Interval (2-Sided) 96%
-3.67 to 7.5
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival
Hide Description Survival time was defined as the number of days from the day the participant was randomly assigned to study treatment to the date of death, regardless of cause.
Time Frame At 676 death events (up to 38 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 408 407
Median (95% Confidence Interval)
Unit of Measure: days
213
(187 to 255)
254
(223 to 282)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SGI-110 (Guadecitabine), Treatment Choice
Comments Overall survival curves were estimated using Kaplan-Meier method and compared between the treatment groups using a 2-sided stratification log-rank test, stratified by the same factors used at randomization: age (<75 or >=75), Eastern Cooperative Oncology Group (ECOG) performance status (0-1, 2-3), study center region (North American, Europe, Rest of World), and secondary AML (secondary to MDS or other antecedent hematologic disorder) or poor-risk cytogenetics (Yes, No/Unknown).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7328
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.83 to 1.14
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Composite CR (CRc)
Hide Description CRc is reported as the number of participants with a best response of CR, complete response with incomplete platelet recovery (CRp), or complete response with incomplete blood count recovery (CRi).
Time Frame Up to 38 months (median follow-up of 25.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens were administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 408 407
Measure Type: Count of Participants
Unit of Measure: Participants
93
  22.8%
91
  22.4%
4.Secondary Outcome
Title Number of Days Alive and Out of the Hospital
Hide Description The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The Number of Days Alive and Out of the Hospital (NDAOH) was calculated as: NDAOH=180 - total duration of all hospital stays within 180 days from the first treatment - number of death days before Day 180. For subjects who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the subject would have died the day after the last contact day.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 408 407
Mean (Standard Deviation)
Unit of Measure: days
98.1  (63.6) 105.7  (63.58)
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Progression-free survival was defined as the number of days from randomization to the earliest date of investigator's assessment of disease progression, participant receiving an alternative anti-leukemia therapy (including hematopoietic cell transplant), or relapse by peripheral blood (PB) assessment or blinded bone marrow (BM) assessment, whichever occurred first, or death, regardless of cause.
Time Frame Up to 38 months (median follow-up of 25.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens were administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 408 407
Median (95% Confidence Interval)
Unit of Measure: days
159
(136 to 178)
166
(148 to 179)
6.Secondary Outcome
Title Number of Red Blood Cell or Platelet Transfusions
Hide Description The total number of red blood cells (RBCs) transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 408 407
Mean (Standard Deviation)
Unit of Measure: transfusion units
Red Blood Cell Transfusions 16.2  (11.84) 15.6  (13.02)
Platelet Transfusions 12.5  (18.78) 14.4  (39.10)
7.Secondary Outcome
Title Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-5D-5L
Hide Description EuroQol 5-level 5-dimension (EQ-5D-5L) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. Scores within each dimension for EQ-5D (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) were calculated using counts and proportions. Mean change in scores from baseline are summarized in which an index score of 0 represents the worst health state and 1 represents the best health state.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 391 378
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 391 participants 378 participants
0.7767  (0.2160) 0.7663  (0.2291)
Month 6 Number Analyzed 180 participants 183 participants
0.8252  (0.1825) 0.8240  (0.1948)
Change from Baseline Number Analyzed 177 participants 178 participants
-0.0023  (0.1830) 0.0112  (0.2325)
8.Secondary Outcome
Title Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-VAS
Hide Description EuroQol-Visual Analogue Scale (EQ-VAS) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. A vertical 20-cm scale for EQ-VAS was used where the lowest value of 0 was labeled "the worst health you can imagine" and the top value of 100 was labeled "the best health you can imagine." Mean change in scores from baseline are summarized.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 391 377
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 391 participants 377 participants
64.64  (21.69) 63.58  (21.05)
Month 6 Number Analyzed 180 participants 183 participants
72.76  (18.61) 71.72  (18.88)
Change from Baseline Number Analyzed 177 participants 178 participants
3.28  (19.35) 3.67  (22.16)
9.Secondary Outcome
Title Duration of CR
Hide Description Duration of CR (in number of days) was calculated from the first time a CR was observed to the time of relapse, defined as the earliest time point whereby BM assessment or PB assessment indicated relapse/disease progression due to reappearance of leukemic blasts in PB or ≥ 5% leukemic blasts in BM.
Time Frame Up to 38 months (median follow-up of 25.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis set includes all randomized participants.
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description:
Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Overall Number of Participants Analyzed 408 407
Median (95% Confidence Interval)
Unit of Measure: days
217
(175 to 261)
231
(182 to 289)
Time Frame Up to 51 months. Median (range) duration of treatment was 5 cycles (1-42) for SGI-110 and 5 cycles (1-37) for Treatment Choice (28 days per cycle). Treatment-emergent adverse events were events that first occurred or worsened after the first dose of study treatment until 30 days after the last dose or start of an alternative anti-leukemia treatment, whichever occurred first.
Adverse Event Reporting Description Safety analysis set (randomized participants who received study treatment) was analyzed for TEAEs. All-cause mortality is presented for all randomized participants (participant flow shows number of deaths with primary reason for study withdrawal). Combining participants into a single group (Treatment Choice) was pre-specified as part of the study design and data for each treatment in that arm were not analyzed separately. Death is listed as an SAE when there is no identifiable cause or event.
 
Arm/Group Title SGI-110 (Guadecitabine) Treatment Choice
Hide Arm/Group Description Guadecitabine 60 mg/m^2 was administered subcutaneously daily for 5 days (Days 1-5) in 28-day cycles. One of the following treatment regimens were administered: 20 mg cytarabine subcutaneously (SC) BID on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
All-Cause Mortality
SGI-110 (Guadecitabine) Treatment Choice
Affected / at Risk (%) Affected / at Risk (%)
Total   341/408 (83.58%)      344/407 (84.52%)    
Hide Serious Adverse Events
SGI-110 (Guadecitabine) Treatment Choice
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   327/401 (81.55%)      297/392 (75.77%)    
Blood and lymphatic system disorders     
Agranulocytosis  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Anemia  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Disseminated intravascular coagulation  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Febrile bone marrow aplasia  1  3/401 (0.75%)  3 4/392 (1.02%)  4
Febrile neutropenia  1  101/401 (25.19%)  147 88/392 (22.45%)  138
Hemorrhagic diathesis  1  2/401 (0.50%)  3 0/392 (0.00%)  0
Histiocytosis hematophagic  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Leukocytosis  1  6/401 (1.50%)  7 2/392 (0.51%)  2
Lymphoadenopathy  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Lymphoadenopathy mediastinal  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Monoclonal B-cell lymphocytosis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Neutropenia  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Pancytopenia  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Splenic infarction  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Thrombocytopenia  1  15/401 (3.74%)  15 5/392 (1.28%)  5
Cardiac disorders     
Acute coronary syndrome  1  3/401 (0.75%)  3 0/392 (0.00%)  0
Acute myocardial infarction  1  3/401 (0.75%)  6 3/392 (0.77%)  3
Angina pectoris  1  3/401 (0.75%)  4 4/392 (1.02%)  4
Arrhythmia  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Atrial fibrillation  1  5/401 (1.25%)  5 6/392 (1.53%)  13
Atrial flutter  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Atrial tachycardia  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Atrioventricular block complete  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Cardiac arrest  1  3/401 (0.75%)  3 9/392 (2.30%)  9
Cardiac failure  1  8/401 (2.00%)  8 10/392 (2.55%)  11
Cardiac failure acute  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Cardiac failure chronic  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Cardiac failure congestive  1  4/401 (1.00%)  7 3/392 (0.77%)  3
Cardiac tamponade  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Cardio-respiratory arrest  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Cardiogenic shock  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Cardiopulmonary failure  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Cardiorenal syndrome  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Cardiovascular insufficiency  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Coronary artery stenosis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Myocardial infarction  1  1/401 (0.25%)  1 3/392 (0.77%)  3
Pericardial effusion  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Pericarditis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Sinus node dysfunction  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Supraventricular tachycardia  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Ear and labyrinth disorders     
Mastoid disorder  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Sudden hearing loss  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Vertigo  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Endocrine disorders     
Diabetes insipidus  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Inappropriate antidiuretic hormone secretion  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Gastrointestinal disorders     
Abdominal pain  1  4/401 (1.00%)  4 2/392 (0.51%)  2
Abdominal pain upper  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Anal fissure  1  1/401 (0.25%)  2 1/392 (0.26%)  1
Anal fistula  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Colitis  1  3/401 (0.75%)  4 2/392 (0.51%)  2
Colitis ischemic  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Constipation  1  2/401 (0.50%)  2 1/392 (0.26%)  2
Diarrhea  1  8/401 (2.00%)  9 7/392 (1.79%)  10
Diverticular perforation  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Diverticulum  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Dyspepsia  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Dysphagia  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Enteritis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Fecaloma  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Gastric hemorrhage  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Gastrointestinal hemorrhage  1  2/401 (0.50%)  3 1/392 (0.26%)  2
Hemorrhoids  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Ileus  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Ileus paralytic  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Incarcerated inguinal hernia  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Intestinal perforation  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Intussusception  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Melaena  1  3/401 (0.75%)  3 2/392 (0.51%)  2
Mesenteric artery thrombosis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Nausea  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Neutropenic colitis  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Esophagitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pancreatitis  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Pneumatosis intestinalis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Proctalgia  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Rectal hemorrhage  1  2/401 (0.50%)  2 4/392 (1.02%)  4
Small intestinal hemorrhage  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Small intestinal obstruction  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Stomatitis  1  3/401 (0.75%)  3 1/392 (0.26%)  1
Tooth disorder  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Vomiting  1  2/401 (0.50%)  2 1/392 (0.26%)  2
General disorders     
Asthenia  1  2/401 (0.50%)  2 4/392 (1.02%)  4
Catheter site erythema  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Chest pain  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Death  1  5/401 (1.25%)  5 5/392 (1.28%)  5
Device related thrombosis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Discomfort  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Fatigue  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Gait disturbance  1  0/401 (0.00%)  0 2/392 (0.51%)  2
General physical health deterioration  1  9/401 (2.24%)  9 10/392 (2.55%)  10
Impaired healing  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Injection site reaction  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Malaise  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Multiple organ dysfunction syndrome  1  5/401 (1.25%)  5 4/392 (1.02%)  4
Non-cardiac chest pain  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Edema peripheral  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pyrexia  1  16/401 (3.99%)  19 13/392 (3.32%)  14
Sudden cardiac death  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Sudden death  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Systemic inflammatory response syndrome  1  1/401 (0.25%)  1 1/392 (0.26%)  2
Hepatobiliary disorders     
Biliary colic  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Cholangitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Cholecystitis acute  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Gallbladder obstruction  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Hepatitis acute  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Ischemic hepatitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Jaundice cholestatic  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Portal vein thrombosis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Immune system disorders     
Anaphylactic reaction  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Infections and infestations     
Abdominal wall abscess  1  1/401 (0.25%)  2 0/392 (0.00%)  0
Abscess intestinal  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Anal abscess  1  3/401 (0.75%)  3 1/392 (0.26%)  1
Appendicitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Arthritis bacterial  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Aspergillus infection  1  3/401 (0.75%)  3 0/392 (0.00%)  0
Atypical pneumonia  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Bacteremia  1  7/401 (1.75%)  8 2/392 (0.51%)  2
Bacterial infection  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Bacteroides bacteremia  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Bronchitis  1  6/401 (1.50%)  6 2/392 (0.51%)  2
Bronchopulmonary aspergillosis  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Campylobacter gastroenteritis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Cellulitis  1  3/401 (0.75%)  4 6/392 (1.53%)  7
Cellulitis orbital  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Cellulitis staphylococcal  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Clostridium colitis  1  1/401 (0.25%)  2 0/392 (0.00%)  0
Clostridium difficile colitis  1  4/401 (1.00%)  4 2/392 (0.51%)  3
Clostridium difficile infection  1  4/401 (1.00%)  5 2/392 (0.51%)  2
Cystitis  1  3/401 (0.75%)  3 0/392 (0.00%)  0
Dermo-hypodermitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Device related infection  1  4/401 (1.00%)  4 7/392 (1.79%)  8
Device related sepsis  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Diverticulitis  1  4/401 (1.00%)  6 1/392 (0.26%)  1
Encephalomyelitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Endocarditis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Enterobacter infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Epiglottitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Erysipelas  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Escherichia bacteremia  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Escherichia infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Escherichia urinary tract infection  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Eye infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Febrile infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Gastric infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Gastroenteritis  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Gastroenteritis pseudomonas  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Gastroenteritis viral  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Gingivitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
H1N1 influenza  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Hematoma infection  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Hepatosplenic abscess  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Herpes simplex  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Herpes zoster  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Herpes zoster oticus  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Infection  1  6/401 (1.50%)  6 5/392 (1.28%)  6
Infectious colitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Influenza  1  6/401 (1.50%)  6 3/392 (0.77%)  3
Injection site abscess  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Injection site cellulitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Injection site infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Kidney infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Klebsiella infection  1  3/401 (0.75%)  3 0/392 (0.00%)  0
Liver abscess  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Localized infection  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Lower respiratory tract infection  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Mastoiditis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Mucormycosis  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Muscle abscess  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Neutropenic infection  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Osteomyelitis  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Otitis media  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Otitis media acute  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Parotitis  1  2/401 (0.50%)  3 0/392 (0.00%)  0
Pathogen resistance  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Periorbital cellulitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Peritonitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Periumbilical abscess  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pharyngitis  1  2/401 (0.50%)  2 1/392 (0.26%)  2
Pneumocystis jirovecii pneumonia  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pneumonia  1  117/401 (29.18%)  147 79/392 (20.15%)  102
Pneumonia cytomegaloviral  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pneumonia influenzal  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pneumonia legionella  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pneumonia pseudomonal  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Post procedural cellulitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Postoperative wound infection  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pseudomembranous colitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pseudomonal sepsis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pseudomonas infection  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Pulmonary tuberculosis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pulpitis dental  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pyelonephritis  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Pyelonephritis acute  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Rectal abscess  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Respiratory syncytial virus infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Respiratory tract infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Scrotal infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Sepsis  1  62/401 (15.46%)  83 44/392 (11.22%)  58
Septic shock  1  16/401 (3.99%)  17 17/392 (4.34%)  19
Septic vasculitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Sinusitis  1  0/401 (0.00%)  0 4/392 (1.02%)  4
Sinusitis fungal  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Skin infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Soft tissue infection  1  3/401 (0.75%)  3 2/392 (0.51%)  2
Staphylococcal bacteremia  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Staphylococcal infection  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Staphylococcal sepsis  1  2/401 (0.50%)  2 3/392 (0.77%)  3
Streptococcal bacteremia  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Systemic candida  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Systemic infection  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Tonsillitis  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Tooth infection  1  2/401 (0.50%)  3 1/392 (0.26%)  1
Tuberculous pleurisy  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Upper respiratory tract infection  1  4/401 (1.00%)  4 1/392 (0.26%)  1
Urethritis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Urinary tract infection  1  14/401 (3.49%)  16 10/392 (2.55%)  11
Urinary tract infection enterococcal  1  3/401 (0.75%)  3 0/392 (0.00%)  0
Urosepsis  1  3/401 (0.75%)  3 0/392 (0.00%)  0
Viral infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Wound infection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Wound infection staphylococcal  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Bronchopulmonary aspergillosis allergic  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Urinary tract infection staphylococcal  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Injury, poisoning and procedural complications     
Allergic transfusion reaction  1  1/401 (0.25%)  2 1/392 (0.26%)  1
Ankle fracture  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Concussion  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Contusion  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Craniocerebral injury  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Fall  1  1/401 (0.25%)  1 2/392 (0.51%)  2
Femur fracture  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Fibula fracture  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Fracture  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Hemolytic transfusion reaction  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Head injury  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Hip fracture  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Humerus fracture  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Infusion related reaction  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Joint dislocation  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pelvic fracture  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Rib fracture  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Spinal compression fracture  1  1/401 (0.25%)  1 2/392 (0.51%)  2
Splenic rupture  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Subarachnoid hemorrhage  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Subdural hematoma  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Subdural hemorrhage  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Tibia fracture  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Transfusion reaction  1  4/401 (1.00%)  4 0/392 (0.00%)  0
Traumatic lung injury  1  0/401 (0.00%)  0 1/392 (0.26%)  2
Upper limb fracture  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Investigations     
Blood bilirubin increased  1  1/401 (0.25%)  1 0/392 (0.00%)  0
C-reactive protein increased  1  3/401 (0.75%)  3 3/392 (0.77%)  3
Influenza A virus test positive  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Metabolism and nutrition disorders     
Decreased appetite  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Dehydration  1  2/401 (0.50%)  2 4/392 (1.02%)  4
Failure to thrive  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Hypercalcemia  1  1/401 (0.25%)  2 0/392 (0.00%)  0
Hyperglycemia  1  1/401 (0.25%)  1 2/392 (0.51%)  2
Hypoglycemia  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Hypokalemia  1  2/401 (0.50%)  2 4/392 (1.02%)  5
Hyponatremia  1  1/401 (0.25%)  1 3/392 (0.77%)  4
Tumor lysis syndrome  1  5/401 (1.25%)  5 2/392 (0.51%)  2
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Back pain  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Bone pain  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Bursitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Intervertebral disc protrusion  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Joint effusion  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Lumbar spinal stenosis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Muscle atrophy  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Muscle hemorrhage  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Musculoskeletal pain  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Neck pain  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Osteoarthritis  1  2/401 (0.50%)  2 2/392 (0.51%)  3
Osteonecrosis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pain in extremity  1  1/401 (0.25%)  1 2/392 (0.51%)  2
Rhabdomyolysis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Shoulder deformity  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Spinal pain  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
B-cell lymphoma  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Basal cell carcinoma  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Bile duct cancer  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Biliary neoplasm  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Central nervous system leukemia  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Chloroma  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Endometrial cancer metastatic  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Kaposi's sarcoma  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Lung adenocarcinoma  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Metastatic squamous cell carcinoma  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Squamous cell carcinoma  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Transitional cell carcinoma  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Tumor associated fever  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Nervous system disorders     
Cerebral hemorrhage  1  1/401 (0.25%)  1 2/392 (0.51%)  2
Cerebrovascular accident  1  6/401 (1.50%)  6 2/392 (0.51%)  2
Depressed level of consciousness  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Epilepsy  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Facial paralysis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Hemorrhage intracranial  1  1/401 (0.25%)  1 4/392 (1.02%)  5
Hemorrhagic stroke  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Headache  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Intracranial hematoma  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Ischemic stroke  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Lethargy  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Nervous system disorder  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Peroneal nerve palsy  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Presyncope  1  0/401 (0.00%)  0 1/392 (0.26%)  2
Seizure  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Syncope  1  2/401 (0.50%)  2 4/392 (1.02%)  6
Transient ischemic attack  1  1/401 (0.25%)  1 2/392 (0.51%)  2
Vocal cord paralysis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Product Issues     
Device dislocation  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Psychiatric disorders     
Confusional state  1  4/401 (1.00%)  4 0/392 (0.00%)  0
Delirium  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Depression  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Personality change  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Suicide attempt  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  11/401 (2.74%)  11 15/392 (3.83%)  16
Chronic kidney disease  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Cystitis hemorrhagic  1  1/401 (0.25%)  2 0/392 (0.00%)  0
Hematuria  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Renal colic  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Renal failure  1  4/401 (1.00%)  4 2/392 (0.51%)  2
Ureterolithiasis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Urinary retention  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Urinary tract obstruction  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary edema  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Acute respiratory distress syndrome  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Acute respiratory failure  1  2/401 (0.50%)  2 6/392 (1.53%)  6
Aspiration  1  1/401 (0.25%)  1 2/392 (0.51%)  2
Asthma  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Chronic obstructive pulmonary disease  1  2/401 (0.50%)  3 1/392 (0.26%)  1
Dyspnea  1  2/401 (0.50%)  2 2/392 (0.51%)  2
Epistaxis  1  3/401 (0.75%)  3 3/392 (0.77%)  3
Hemoptysis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Interstitial lung disease  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Laryngeal inflammation  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Laryngeal edema  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Organizing pneumonia  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Oropharyngeal pain  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pleural effusion  1  6/401 (1.50%)  7 3/392 (0.77%)  3
Pleuritic pain  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Pneumonia aspiration  1  1/401 (0.25%)  1 1/392 (0.26%)  1
Pneumonitis  1  3/401 (0.75%)  3 0/392 (0.00%)  0
Pulmonary alveolar hemorrhage  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pulmonary embolism  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Pulmonary hemorrhage  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Pulmonary mass  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pulmonary edema  1  5/401 (1.25%)  5 1/392 (0.26%)  1
Respiratory distress  1  2/401 (0.50%)  2 1/392 (0.26%)  1
Respiratory failure  1  5/401 (1.25%)  5 2/392 (0.51%)  2
Stridor  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Skin and subcutaneous tissue disorders     
Acute febrile neutrophilic dermatosis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Angioedema  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Dermatitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Eczema  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Hypersensitivity vasculitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Pyoderma gangrenosum  1  1/401 (0.25%)  3 0/392 (0.00%)  0
Rash generalized  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Rash maculo-papular  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Skin disorder  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Skin ulcer  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Toxic skin eruption  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Vascular disorders     
Aortic aneurysm  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Aortic dissection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Artery dissection  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Circulatory collapse  1  5/401 (1.25%)  5 4/392 (1.02%)  4
Deep vein thrombosis  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Hematoma  1  3/401 (0.75%)  3 1/392 (0.26%)  2
Hypertension  1  0/401 (0.00%)  0 2/392 (0.51%)  2
Hypotension  1  2/401 (0.50%)  2 3/392 (0.77%)  3
Iliac artery embolism  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Leriche syndrome  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Lupus vasculitis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Orthostatic hypotension  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Peripheral arterial occlusive disease  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Phlebitis  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Shock  1  1/401 (0.25%)  1 0/392 (0.00%)  0
Shock hemorrhagic  1  0/401 (0.00%)  0 1/392 (0.26%)  1
Thrombophlebitis  1  2/401 (0.50%)  2 0/392 (0.00%)  0
Venous thrombosis  1  0/401 (0.00%)  0 1/392 (0.26%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SGI-110 (Guadecitabine) Treatment Choice
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   379/401 (94.51%)      371/392 (94.64%)    
Blood and lymphatic system disorders     
Anemia  1  88/401 (21.95%)  211 78/392 (19.90%)  201
Febrile neutropenia  1  66/401 (16.46%)  103 40/392 (10.20%)  57
Leukopenia  1  37/401 (9.23%)  120 33/392 (8.42%)  124
Neutropenia  1  115/401 (28.68%)  319 88/392 (22.45%)  233
Thrombocytopenia  1  116/401 (28.93%)  380 101/392 (25.77%)  313
Gastrointestinal disorders     
Abdominal pain  1  30/401 (7.48%)  43 46/392 (11.73%)  50
Abdominal pain upper  1  21/401 (5.24%)  25 15/392 (3.83%)  16
Constipation  1  125/401 (31.17%)  166 114/392 (29.08%)  168
Diarrhea  1  122/401 (30.42%)  169 83/392 (21.17%)  116
Hemorrhoids  1  24/401 (5.99%)  28 19/392 (4.85%)  24
Nausea  1  91/401 (22.69%)  141 108/392 (27.55%)  150
Stomatitis  1  46/401 (11.47%)  59 38/392 (9.69%)  44
Vomiting  1  58/401 (14.46%)  80 66/392 (16.84%)  82
General disorders     
Asthenia  1  61/401 (15.21%)  102 55/392 (14.03%)  81
Fatigue  1  63/401 (15.71%)  97 50/392 (12.76%)  74
Injection site reaction  1  73/401 (18.20%)  148 48/392 (12.24%)  75
Edema peripheral  1  95/401 (23.69%)  125 78/392 (19.90%)  108
Pain  1  21/401 (5.24%)  22 14/392 (3.57%)  14
Pyrexia  1  89/401 (22.19%)  155 110/392 (28.06%)  176
Infections and infestations     
Bronchitis  1  22/401 (5.49%)  30 13/392 (3.32%)  15
Cellulitis  1  29/401 (7.23%)  37 22/392 (5.61%)  25
Nasopharyngitis  1  18/401 (4.49%)  27 20/392 (5.10%)  21
Oral candidiasis  1  23/401 (5.74%)  27 17/392 (4.34%)  21
Oral herpes  1  31/401 (7.73%)  36 20/392 (5.10%)  21
Pneumonia  1  54/401 (13.47%)  64 31/392 (7.91%)  34
Upper respiratory tract infection  1  22/401 (5.49%)  34 20/392 (5.10%)  28
Urinary tract infection  1  33/401 (8.23%)  46 28/392 (7.14%)  39
Injury, poisoning and procedural complications     
Contusion  1  20/401 (4.99%)  23 22/392 (5.61%)  27
Fall  1  34/401 (8.48%)  43 29/392 (7.40%)  37
Investigations     
Weight decreased  1  35/401 (8.73%)  47 25/392 (6.38%)  28
Metabolism and nutrition disorders     
Decreased appetite  1  89/401 (22.19%)  116 62/392 (15.82%)  80
Hyperkalemia  1  24/401 (5.99%)  33 13/392 (3.32%)  19
Hypoalbuminemia  1  26/401 (6.48%)  36 23/392 (5.87%)  43
Hypocalcemia  1  25/401 (6.23%)  30 18/392 (4.59%)  29
Hypokalemia  1  96/401 (23.94%)  173 77/392 (19.64%)  128
Hypomagnesemia  1  31/401 (7.73%)  50 27/392 (6.89%)  36
Musculoskeletal and connective tissue disorders     
Arthralgia  1  24/401 (5.99%)  28 35/392 (8.93%)  39
Back pain  1  34/401 (8.48%)  43 36/392 (9.18%)  43
Musculoskeletal pain  1  17/401 (4.24%)  20 20/392 (5.10%)  22
Pain in extremity  1  40/401 (9.98%)  51 32/392 (8.16%)  39
Nervous system disorders     
Dizziness  1  36/401 (8.98%)  47 42/392 (10.71%)  56
Headache  1  32/401 (7.98%)  44 38/392 (9.69%)  53
Psychiatric disorders     
Anxiety  1  23/401 (5.74%)  23 22/392 (5.61%)  24
Depression  1  14/401 (3.49%)  15 21/392 (5.36%)  21
Insomnia  1  38/401 (9.48%)  52 45/392 (11.48%)  56
Renal and urinary disorders     
Acute kidney injury  1  23/401 (5.74%)  24 16/392 (4.08%)  17
Respiratory, thoracic and mediastinal disorders     
Cough  1  79/401 (19.70%)  100 66/392 (16.84%)  83
Dyspnea  1  63/401 (15.71%)  83 51/392 (13.01%)  60
Epistaxis  1  53/401 (13.22%)  71 36/392 (9.18%)  51
Oropharyngeal pain  1  22/401 (5.49%)  29 23/392 (5.87%)  27
Pleural effusion  1  21/401 (5.24%)  23 13/392 (3.32%)  13
Skin and subcutaneous tissue disorders     
Erythema  1  21/401 (5.24%)  21 17/392 (4.34%)  20
Pruritis  1  22/401 (5.49%)  28 26/392 (6.63%)  32
Rash  1  41/401 (10.22%)  55 28/392 (7.14%)  33
Vascular disorders     
Hematoma  1  25/401 (6.23%)  33 19/392 (4.85%)  29
Hypertension  1  28/401 (6.98%)  42 25/392 (6.38%)  37
Hypotension  1  31/401 (7.73%)  40 31/392 (7.91%)  37
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Harold Keer
Organization: Astex Pharmaceuticals, Inc.
Phone: 925-560-2913
EMail: harold.keer@astx.com
Layout table for additonal information
Responsible Party: Astex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02348489    
Other Study ID Numbers: SGI-110-04
First Submitted: January 22, 2015
First Posted: January 28, 2015
Results First Submitted: November 11, 2020
Results First Posted: January 14, 2021
Last Update Posted: January 14, 2021