ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 24 of 30 for:    Guatemala | Dominican Republic

Long-term Safety of Alogliptin in Patients With Type 2 Diabetes Mellitus

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: NCT00306384
Recruitment Status : Completed
First Posted : March 23, 2006
Results First Posted : March 22, 2013
Last Update Posted : March 22, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus
Intervention Drug: Alogliptin
Enrollment 3323

Recruitment Details Patients who completed 1 of the following 7 studies took part in the study at 423 investigative sites worldwide: SYR-322-PLC-010 (NCT00286455); SYR-322-SULF-007 (NCT00286468); SYR-322-MET-008 (NCT00286442); SYR-322-TZD-009 (NCT00286494); SYR-322-INS-011 (NCT00286429); 01-05-TL-322OPI-001 (NCT00328627); 01-06-TL-322OPI-002 (NCT00395512).
Pre-assignment Details Patients who had previously completed 1 of 7 double-blind alogliptin studies were randomized (1:1) to either 12.5 or 25 mg once daily alogliptin. Patients who were rescued during their previous double-blind study in response to protocol-defined hyperglycemic rescue criteria were assigned to alogliptin 25 mg.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years. Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years. Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Period Title: Overall Study
Started 1396 1399 528
Safety Set 1395 [1] 1398 [1] 527 [1]
Completed 854 891 251
Not Completed 542 508 277
Reason Not Completed
Adverse Event             103             87             40
Major protocol deviation             43             51             18
Lost to Follow-up             57             41             35
Voluntary withdrawal             199             187             91
Study termination             1             0             1
Pregnancy             3             1             1
Lack of Efficacy             26             40             38
Investigator discretion             28             31             21
Other             80             70             32
Site closure             2             0             0
[1]
Patients who received at least one dose of study drug
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg Total
Hide Arm/Group Description Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years. Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years. Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years. Total of all reporting groups
Overall Number of Baseline Participants 1396 1399 528 3323
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1396 participants 1399 participants 528 participants 3323 participants
55.8  (9.92) 55.1  (10.21) 53.0  (10.06) 55.0  (10.11)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1396 participants 1399 participants 528 participants 3323 participants
<65 years 1134 1134 461 2729
≥65 years 262 265 67 594
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1396 participants 1399 participants 528 participants 3323 participants
Female
699
  50.1%
730
  52.2%
289
  54.7%
1718
  51.7%
Male
697
  49.9%
669
  47.8%
239
  45.3%
1605
  48.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1396 participants 1399 participants 528 participants 3323 participants
American Indian or Alaska Native 8 3 2 13
Asian 120 108 32 260
Native Hawaiian or Other Pacific Islander 2 0 1 3
Black or African American 65 88 34 187
White 1025 1007 390 2422
Other 176 193 69 438
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 1396 participants 1399 participants 528 participants 3323 participants
31.42  (5.370) 31.71  (5.266) 32.20  (5.704) 31.66  (5.386)
Diabetes duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1396 participants 1399 participants 528 participants 3323 participants
6.56  (5.446) 6.92  (5.824) 8.35  (6.325) 6.99  (5.784)
Previous double-blind study treatment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1396 participants 1399 participants 528 participants 3323 participants
Placebo 118 110 135 363
Alogliptin 12.5 mg 274 262 105 641
Alogliptin 25 mg 243 262 99 604
Study 01-05-TL-322OPI-001 546 548 146 1240
Study 01-06-TL-322OPI-002 215 217 43 475
[1]
Measure Description: Patients from coadministration Studies 01-05-TL-322OPI-001 and 01-06-TL-322OPI-002 are presented separately; due to the complexity of treatment assignments, they were not included in the subgroups of patients previously randomized to placebo, alogliptin 12.5 mg, or alogliptin 25 mg.
1.Primary Outcome
Title Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Hide Description Safety was assessed by physical examinations, clinical laboratory parameters, electrocardiogram (ECG) readings, vital sign measurements, oral temperature, and hypoglycemic events. Changes in laboratory values or ECG parameters were considered to be adverse events if they were judged to be clinically significant. A TEAE was any event that started on or after the first dose of open-label study drug and within 14 days after the last dose.
Time Frame 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 1394 1399 527
Measure Type: Number
Unit of Measure: percentage of participants
Any treatment emergent adverse event (TEAE) 87.2 87.1 84.6
Study drug-related TEAE 25.6 22.7 24.9
TEAE leading to discontinuation 7.0 6.1 7.6
Treatment emergent serious AE 16.7 16.3 15.7
Study drug-related serious AE 2.6 2.1 1.9
Treatment-emergent deaths 1.4 1.0 0.9
2.Secondary Outcome
Title Change From Baseline Over Time in Glycosylated Hemoglobin
Hide Description The change from Baseline in glycosylated hemoglobin (HbA1c; the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) during the study. Endpoint was defined as the last postbaseline observation collected within 7 days after the last dose of open-label study drug.
Time Frame Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set where data were available.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 1395 1398 527
Mean (Standard Deviation)
Unit of Measure: percent glycosylated hemoglobin
Baseline (n=1362, 1359, 501) 7.21  (0.815) 7.22  (0.814) 9.30  (0.900)
Week 12 change from Baseline (n=1290, 1286, 463) 0.18  (0.635) 0.14  (0.632) -0.52  (1.064)
Month 6 change from Baseline (n= 1236, 1252, 433) 0.31  (0.859) 0.26  (0.848) -0.73  (1.285)
Month 9 change from Baseline (n=1217, 1231, 413) 0.34  (0.969) 0.33  (0.894) -0.78  (1.282)
Month 12 change from Baseline (1175, 1182, 388) 0.41  (1.010) 0.41  (0.952) -0.78  (1.309)
Month 15 change from Baseline (n=1119, 1133, 374) 0.47  (0.990) 0.48  (1.068) -0.75  (1.332)
Month 18 change from Baseline (n=1111, 1095, 350) 0.50  (1.082) 0.50  (1.047) -0.70  (1.320)
Month 21 change from Baseline (n=1061, 1071, 338) 0.52  (1.096) 0.51  (1.070) -0.75  (1.389)
Month 24 change from Baseline (n=1027, 1039, 320) 0.53  (1.111) 0.58  (1.107) -0.69  (1.417)
Month 27 change from Baseline (n=991, 1002, 300) 0.58  (1.124) 0.58  (1.159) -0.71  (1.349)
Month 30 change from Baseline (n=944, 955, 281) 0.57  (1.127) 0.57  (1.167) -0.78  (1.361)
Month 33 change from Baseline (n=923, 941, 276) 0.55  (1.181) 0.57  (1.196) -0.73  (1.418)
Month 36 change from Baseline (n=882, 931, 274) 0.54  (1.215) 0.55  (1.141) -0.80  (1.411)
Month 39 change from Baseline (n=886, 913, 259) 0.56  (1.223) 0.56  (1.216) -0.73  (1.431)
Month 42 change from Baseline (n=854, 891, 252) 0.59  (1.225) 0.54  (1.221) -0.78  (1.492)
Month 45 change from Baseline (n=866, 902, 253) 0.61  (1.250) 0.56  (1.242) -0.70  (1.398)
Endpoint change from Baseline (n=1362, 1359, 501) 1.63  (1.310) 0.61  (1.261) -0.42  (1.448)
3.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose
Hide Description The change from Baseline in fasting plasma glucose (FPG) at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Time Frame Baseline and Year 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set where data were available.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 1388 1386 517
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 144.4  (41.64) 142.6  (39.41) 215.3  (60.25)
Change from Baseline 14.8  (56.25) 14.9  (53.46) -26.4  (84.51)
4.Secondary Outcome
Title Percentage of Participants With Marked Hyperglycemia
Hide Description

Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (≥11.10 mmol/L).

The Month 42 to Month 45 interval includes all marked hyperglycemic episodes occurring on or after Day 1247 (a 203-day visit window).

Time Frame Randomization up to 4 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set where data were available.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 1395 1398 527
Measure Type: Number
Unit of Measure: percentage of participants
Day 1 to <Week 2 (n=1299, 1290, 481) 9.1 8.0 55.5
Week 2 to <Week 4 (n=1286, 1306, 481) 11.5 10.2 45.9
Week 4 to <Week 8 (n=1303, 1331, 490) 9.2 11.0 46.1
Week 8 to <Week 12 (n=1331, 1347, 495) 11.5 10.8 41.0
Week 12 to <Month 6 (n=1329, 1338, 480) 12.0 11.6 39.4
Month 6 to <Month 9 (n=1286, 1289, 448) 12.8 10.7 36.8
Month 9 to <Month 12 (n=1252, 1260, 425) 11.4 12.9 32.5
Month 12 to <Month 15 (n=1210, 1217, 409) 13.1 13.0 29.3
Month 15 to <Month 18 (n=1157, 1166, 389) 12.7 13.8 27.8
Month 18 to <Month 21 (n=1128, 1128, 365) 11.7 11.6 26.8
Month 21 to <Month 24 (n=1094,1099, 357) 11.2 11.5 26.3
Month 24 to <Month 27 (n=1046, 1066, 334) 11.6 12.3 24.9
Month 27 to <Month 30 (n=1010, 1028, 316) 12.6 11.8 24.7
Month 30 to <Month 33 (n=981, 988, 299) 11.6 11.7 19.7
Month 33 to <Month 36 (n=945, 959, 289) 11.5 12.3 23.5
Month 36 to <Month 39 (n=920, 949, 281) 13.2 12.5 21.0
Month 39 to <Month 42 (n=899, 934, 267) 13.7 13.1 19.5
Month 42 to Month 45 (n=889, 921, 261) 25.5 23.9 39.1
Overall (n= 1389, 1392, 518) 49.7 50.7 87.6
5.Secondary Outcome
Title Change From Baseline in Proinsulin Level
Hide Description

Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.

Note: A transcription error occurred in the reporting of 1 proinsulin value for a patient in the alogliptin 25 mg completed group, for whom a partial patient ID number was mistakenly entered as an end-of-treatment proinsulin level.

Time Frame Baseline and Year 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set where data were available.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 1277 1263 393
Mean (Standard Deviation)
Unit of Measure: pmol/L
Baseline 26.1  (25.99) 25.4  (30.28) 40.2  (36.47)
Change from Baseline 4.1  (27.09) 39.7  (1243.37) -3.3  (31.45)
6.Secondary Outcome
Title Change From Baseline in Insulin Level
Hide Description The change from Baseline in fasting insulin at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Time Frame Baseline and Year 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set where data was available. Does not include patients enrolled in Protocol 01-05-TL-OPI322-001 or Protocol 01-06-TL-OPI322-002.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 537 526 212
Mean (Standard Deviation)
Unit of Measure: μIU/mL
Baseline 15.19  (9.898) 15.50  (12.608) 18.64  (15.845)
Change from Baseline 2.45  (42.706) 2.13  (16.496) 5.62  (23.197)
7.Secondary Outcome
Title Change From Baseline in C-peptide Level
Hide Description C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Time Frame Baseline and Year 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set where data was available. Patients enrolled in Protocol 01-05-TL-OPI322-001 or Protocol 01-06-TL-OPI322-002 are not included.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 615 615 322
Mean (Standard Deviation)
Unit of Measure: ng/mL
Baseline 3.406  (1.5115) 3.323  (1.5945) 3.572  (1.7531)
Change from Baseline -0.471  (1.6464) -0.439  (1.2783) -0.641  (1.5804)
8.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description Change from Baseline in body weight to the last post-baseline observation collected within 7 days after the last dose of open-label study drug.
Time Frame Baseline and Year 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set for whom data was available.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 1387 1385 518
Mean (Standard Deviation)
Unit of Measure: kg
Baseline 86.12  (19.376) 86.61  (19.185) 88.62  (20.947)
Change from Baseline -0.64  (5.283) -0.61  (5.428) 0.25  (5.036)
9.Secondary Outcome
Title Percentage of Participants With a Clinical Response
Hide Description

Clinical response was defined based on the absolute value of HbA1c meeting one of two clinical targets at any post-baseline visit:

  • HbA1c ≤6.5%;
  • HbA1c ≤7.0%.
Time Frame Weeks 2, 4, 8, 12, every 3 months up to 4 years, and 1 Day after final dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety set.
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description:
Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years.
Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
Overall Number of Participants Analyzed 1395 1398 527
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c ≤6.5% 34.8 34.1 11.0
HbA1c ≤7.0% 64.1 65.5 27.1
Time Frame Treatment-emergent adverse events (AEs) were defined as any AEs that started on or after the date of the first dose of open-label study drug and within 14 days after the date of the last dose of open-label study drug.
Adverse Event Reporting Description At each study visit, the investigator assessed whether any events had occurred. Participants could report events at any other time during the study.
 
Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Hide Arm/Group Description Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years. Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years. Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years.
All-Cause Mortality
Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   233/1394 (16.71%)   228/1399 (16.30%)   83/527 (15.75%) 
Blood and lymphatic system disorders       
Anaemia  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Iron deficiency anaemia  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Cardiac disorders       
Acute myocardial infarction  1  7/1394 (0.50%)  11/1399 (0.79%)  4/527 (0.76%) 
Coronary artery disease  1  5/1394 (0.36%)  7/1399 (0.50%)  5/527 (0.95%) 
Myocardial infarction  1  5/1394 (0.36%)  6/1399 (0.43%)  4/527 (0.76%) 
Angina pectoris  1  5/1394 (0.36%)  5/1399 (0.36%)  2/527 (0.38%) 
Angina unstable  1  6/1394 (0.43%)  3/1399 (0.21%)  2/527 (0.38%) 
Myocardial ischaemia  1  7/1394 (0.50%)  3/1399 (0.21%)  0/527 (0.00%) 
Atrial fibrillation  1  1/1394 (0.07%)  4/1399 (0.29%)  1/527 (0.19%) 
Acute coronary syndrome  1  2/1394 (0.14%)  1/1399 (0.07%)  2/527 (0.38%) 
Cardiac failure congestive  1  0/1394 (0.00%)  2/1399 (0.14%)  2/527 (0.38%) 
Ischaemic cardiomyopathy  1  1/1394 (0.07%)  2/1399 (0.14%)  1/527 (0.19%) 
Cardiac failure  1  1/1394 (0.07%)  2/1399 (0.14%)  0/527 (0.00%) 
Cardio-respiratory arrest  1  1/1394 (0.07%)  2/1399 (0.14%)  0/527 (0.00%) 
Atrioventricular block complete  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Atrioventricular block second degree  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Coronary artery stenosis  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Pericardial effusion  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Tachycardia  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Ventricular extrasystoles  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Aortic valve stenosis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Arteriosclerosis coronary artery  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Bradycardia  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Cardiomyopathy  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Cardiopulmonary failure  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Congestive cardiomyopathy  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Coronary artery insufficiency  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Hypertensive heart disease  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Left ventricular dysfunction  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Palpitations  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pericarditis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Sick sinus syndrome  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Congenital, familial and genetic disorders       
MELAS syndrome  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Endocrine disorders       
Goitre  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Hyperthyroidism  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Eye disorders       
Cataract  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Retinal vein thrombosis  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Diabetic retinopathy  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Glaucoma  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Iridocyclitis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Retinal artery occlusion  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Retinal detachment  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Vitreous haemorrhage  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Gastrointestinal disorders       
Pancreatitis  1  1/1394 (0.07%)  4/1399 (0.29%)  1/527 (0.19%) 
Inguinal hernia  1  3/1394 (0.22%)  0/1399 (0.00%)  1/527 (0.19%) 
Abdominal pain  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Diarrhoea  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Gastric ulcer haemorrhage  1  1/1394 (0.07%)  2/1399 (0.14%)  0/527 (0.00%) 
Pancreatitis acute  1  3/1394 (0.22%)  0/1399 (0.00%)  0/527 (0.00%) 
Gastric ulcer  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Gastritis  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Gastrointestinal haemorrhage  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Umbilical hernia  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Abdominal hernia  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Abdominal pain upper  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Anal fistula  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Colitis ischaemic  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Diverticulum intestinal haemorrhagic  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Duodenal ulcer  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Duodenal ulcer haemorrhage  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Dyspepsia  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Gastrointestinal hypomotility  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Gastrointestinal necrosis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Haematemesis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Haemorrhoids  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Hernial eventration  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Intestinal obstruction  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Intra-abdominal haemorrhage  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pancreatitis relapsing  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Peptic ulcer  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Peritonitis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Rectal polyp  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Rectal prolapse  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Salivary duct inflammation  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Small intestinal obstruction  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
General disorders       
Non-cardiac chest pain  1  4/1394 (0.29%)  4/1399 (0.29%)  2/527 (0.38%) 
Chest pain  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Pyrexia  1  0/1394 (0.00%)  0/1399 (0.00%)  2/527 (0.38%) 
Death  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Influenza like illness  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Hepatobiliary disorders       
Cholelithiasis  1  3/1394 (0.22%)  4/1399 (0.29%)  2/527 (0.38%) 
Cholecystitis acute  1  4/1394 (0.29%)  2/1399 (0.14%)  1/527 (0.19%) 
Cholecystitis  1  1/1394 (0.07%)  2/1399 (0.14%)  0/527 (0.00%) 
Bile duct stone  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Biliary colic  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Cholangitis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Hepatitis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Perforation bile duct  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Immune system disorders       
Allergic oedema  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Allergy to arthropod sting  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Infections and infestations       
Pneumonia  1  13/1394 (0.93%)  6/1399 (0.43%)  0/527 (0.00%) 
Cellulitis  1  4/1394 (0.29%)  3/1399 (0.21%)  4/527 (0.76%) 
Urinary tract infection  1  5/1394 (0.36%)  4/1399 (0.29%)  0/527 (0.00%) 
Erysipelas  1  2/1394 (0.14%)  3/1399 (0.21%)  0/527 (0.00%) 
Osteomyelitis  1  3/1394 (0.22%)  1/1399 (0.07%)  1/527 (0.19%) 
Diverticulitis  1  2/1394 (0.14%)  2/1399 (0.14%)  0/527 (0.00%) 
Gastroenteritis  1  1/1394 (0.07%)  2/1399 (0.14%)  1/527 (0.19%) 
Gangrene  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Postoperative wound infection  1  1/1394 (0.07%)  1/1399 (0.07%)  1/527 (0.19%) 
Abscess limb  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Appendicitis  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Bronchitis  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Bronchopneumonia  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Dengue fever  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Diabetic foot infection  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Infected skin ulcer  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Lobar pneumonia  1  0/1394 (0.00%)  0/1399 (0.00%)  2/527 (0.38%) 
Lower respiratory tract infection  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Post procedural infection  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Pyelonephritis  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Staphylococcal infection  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Viral infection  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Acquired immunodeficiency syndrome  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Appendicitis perforated  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Arthritis bacterial  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Cholecystitis infective  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Coccidioidomycosis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Endophthalmitis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Gastroenteritis viral  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Giardiasis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Helicobacter gastritis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Hepatitis A  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Herpes zoster  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Labyrinthitis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lymphangitis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Nosocomial infection  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Peritonsillar abscess  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Pneumococcal sepsis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pneumonia cryptococcal  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pneumonia pneumococcal  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pulmonary tuberculosis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Pyelonephritis acute  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pyelonephritis chronic  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Pyoderma  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Rectal abscess  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Septic shock  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Sialoadenitis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Subcutaneous abscess  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Tooth abscess  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Typhoid fever  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Urosepsis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Wound infection  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Wound sepsis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Injury, poisoning and procedural complications       
Fall  1  3/1394 (0.22%)  1/1399 (0.07%)  1/527 (0.19%) 
Hip fracture  1  1/1394 (0.07%)  3/1399 (0.21%)  0/527 (0.00%) 
Head injury  1  0/1394 (0.00%)  3/1399 (0.21%)  0/527 (0.00%) 
Subdural haematoma  1  2/1394 (0.14%)  0/1399 (0.00%)  1/527 (0.19%) 
Ankle fracture  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Clavicle fracture  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Femur fracture  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Humerus fracture  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Incisional hernia  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Multiple fractures  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Patella fracture  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Rib fracture  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Tendon injury  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Tendon rupture  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Tibia fracture  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Anaemia postoperative  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Chest injury  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Device occlusion  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Femoral neck fracture  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Foreign body trauma  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Hand fracture  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Incisional hernia, obstructive  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Laceration  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lower limb fracture  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lumbar vertebral fracture  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Multiple injuries  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Post procedural complication  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Radius fracture  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Road traffic accident  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Thermal burn  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Traumatic fracture  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Metabolism and nutrition disorders       
Hyperglycaemia  1  1/1394 (0.07%)  3/1399 (0.21%)  3/527 (0.57%) 
Diabetic foot  1  1/1394 (0.07%)  3/1399 (0.21%)  0/527 (0.00%) 
Dehydration  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Hyperkalaemia  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Hypertriglyceridaemia  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Hyponatraemia  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Obesity  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Hypoglycaemic seizure  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  3/1394 (0.22%)  6/1399 (0.43%)  1/527 (0.19%) 
Rotator cuff syndrome  1  1/1394 (0.07%)  6/1399 (0.43%)  1/527 (0.19%) 
Intervertebral disc protrusion  1  3/1394 (0.22%)  3/1399 (0.21%)  0/527 (0.00%) 
Musculoskeletal chest pain  1  2/1394 (0.14%)  3/1399 (0.21%)  0/527 (0.00%) 
Arthralgia  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Back pain  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Arthritis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Chondromalacia  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Intervertebral disc degeneration  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Intervertebral disc disorder  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lumbar spinal stenosis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Muscle disorder  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Muscular weakness  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Myopathy  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Osteochondrosis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Rhabdomyolysis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Spondylolisthesis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Synovitis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Tendon calcification  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  2/1394 (0.14%)  3/1399 (0.21%)  2/527 (0.38%) 
Uterine leiomyoma  1  1/1394 (0.07%)  3/1399 (0.21%)  0/527 (0.00%) 
Basal cell carcinoma  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Breast cancer female  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Meningioma  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Prostate cancer  1  2/1394 (0.14%)  0/1399 (0.00%)  1/527 (0.19%) 
Rectal cancer  1  1/1394 (0.07%)  2/1399 (0.14%)  0/527 (0.00%) 
Brain neoplasm  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Lung neoplasm  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Lung neoplasm malignant  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Ovarian adenoma  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Pancreatic carcinoma  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Thyroid cancer  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Acute leukaemia  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Adrenal adenoma  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
B-cell lymphoma  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Benign neoplasm of adrenal gland  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Bladder transitional cell carcinoma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Brain neoplasm benign  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Breast cancer stage I  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Breast cancer stage III  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Carcinoid tumour of the appendix  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Central nervous system neoplasm  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Cervix carcinoma stage 0  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Cervix neoplasm  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Choroid melanoma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Chronic lymphocytic leukaemia  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Colon cancer  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Colon cancer stage III  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Colorectal cancer  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Focal nodular hyperplasia  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Gastrointestinal stromal tumour  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Haemangioma of liver  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Hepatic neoplasm malignant  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Langerhans' cell granulomatosis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lung adenocarcinoma  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lung cancer metastatic  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Malignant melanoma in situ  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Mantle cell lymphoma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Mesothelioma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Metastases to liver  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Metastases to peritoneum  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Multiple myeloma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Neuroendocrine tumour  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Non-Hodgkin's lymphoma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Non-small cell lung cancer metastatic  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Oesophageal adenocarcinoma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Oligodendroglioma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Ovarian cancer  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Ovarian germ cell teratoma benign  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Prostatic adenom  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Renal cell carcinoma  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Renal neoplasm  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Squamous cell carcinoma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Thyroid neoplasm  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Transitional cell carcinoma  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  6/1394 (0.43%)  1/1399 (0.07%)  4/527 (0.76%) 
Ischaemic stroke  1  6/1394 (0.43%)  1/1399 (0.07%)  1/527 (0.19%) 
Syncope  1  4/1394 (0.29%)  1/1399 (0.07%)  0/527 (0.00%) 
Carotid artery stenosis  1  0/1394 (0.00%)  3/1399 (0.21%)  0/527 (0.00%) 
Convulsion  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Loss of consciousness  1  3/1394 (0.22%)  0/1399 (0.00%)  0/527 (0.00%) 
Transient ischaemic attack  1  2/1394 (0.14%)  0/1399 (0.00%)  1/527 (0.19%) 
Cerebral ischaemia  1  0/1394 (0.00%)  1/1399 (0.07%)  1/527 (0.19%) 
Dizziness  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Haemorrhage intracranial  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Altered state of consciousness  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Amnesia  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Brain stem syndrome  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Carpal tunnel syndrome  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Cerebral artery occlusion  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Diabetic mononeuropathy  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Diabetic neuropathy  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Dysarthria  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Embolic stroke  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Facial palsy  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Grand mal convulsion  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Haemorrhagic stroke  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Hydrocephalus  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lacunar infarction  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Normal pressure hydrocephalus  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Presyncope  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Radial nerve palsy  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Reversible ischaemic neurological deficit  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Subarachnoid haemorrhage  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Vascular headache  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous incomplete  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Ectopic pregnancy  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Psychiatric disorders       
Major depression  1  0/1394 (0.00%)  2/1399 (0.14%)  0/527 (0.00%) 
Anxiety  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Anxiety disorder  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Hypnagogic hallucination  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Mental disorder  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Panic attack  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Suicide attempt  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Renal and urinary disorders       
Renal failure acute  1  2/1394 (0.14%)  7/1399 (0.50%)  1/527 (0.19%) 
Nephrolithiasis  1  2/1394 (0.14%)  5/1399 (0.36%)  1/527 (0.19%) 
Calculus ureteric  1  3/1394 (0.22%)  1/1399 (0.07%)  1/527 (0.19%) 
Renal colic  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Haematuria  1  1/1394 (0.07%)  0/1399 (0.00%)  1/527 (0.19%) 
Calculus urethral  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Diabetic nephropathy  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Postrenal failure  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Renal failure  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Renal failure chronic  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Stress urinary incontinence  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Tubulointerstitial nephritis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Urinary retention  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Reproductive system and breast disorders       
Menorrhagia  1  0/1394 (0.00%)  3/1399 (0.21%)  1/527 (0.19%) 
Ovarian cyst  1  1/1394 (0.07%)  3/1399 (0.21%)  0/527 (0.00%) 
Benign prostatic hyperplasia  1  1/1394 (0.07%)  2/1399 (0.14%)  0/527 (0.00%) 
Colpocele  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Endometrial hyperplasia  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Genital prolapse  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Breast calcifications  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Epididymal cyst  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Erectile dysfunction  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Fallopian tube cyst  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Menometrorrhagia  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Metrorrhagia  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Pelvic pain  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Uterine polyp  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Uterine prolapse  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Vocal cord polyp  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  2/1394 (0.14%)  2/1399 (0.14%)  0/527 (0.00%) 
Acute pulmonary oedema  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Asthma  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Dyspnoea  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Pleural effusion  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Pulmonary oedema  1  1/1394 (0.07%)  1/1399 (0.07%)  0/527 (0.00%) 
Acute respiratory failure  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Asphyxia  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Asthmatic crisis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Epistaxis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Lung disorder  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pleurisy  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pneumonia aspiration  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Pulmonary embolism  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Pulmonary hypertension  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Respiratory failure  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Sleep apnoea syndrome  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Skin and subcutaneous tissue disorders       
Angioedema  1  1/1394 (0.07%)  1/1399 (0.07%)  1/527 (0.19%) 
Skin ulcer  1  2/1394 (0.14%)  0/1399 (0.00%)  1/527 (0.19%) 
Dermatitis allergic  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Drug eruption  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Rash  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Skin necrosis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Urticaria  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Surgical and medical procedures       
Knee arthroplasty  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  2/1394 (0.14%)  1/1399 (0.07%)  0/527 (0.00%) 
Peripheral vascular disorder  1  1/1394 (0.07%)  1/1399 (0.07%)  1/527 (0.19%) 
Hypertension  1  2/1394 (0.14%)  0/1399 (0.00%)  0/527 (0.00%) 
Arteriosclerosis  1  0/1394 (0.00%)  1/1399 (0.07%)  0/527 (0.00%) 
Hypertensive crisis  1  1/1394 (0.07%)  0/1399 (0.00%)  0/527 (0.00%) 
Pelvic venous thrombosis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Venous thrombosis  1  0/1394 (0.00%)  0/1399 (0.00%)  1/527 (0.19%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   876/1394 (62.84%)   898/1399 (64.19%)   333/527 (63.19%) 
Gastrointestinal disorders       
Diarrhoea  1  108/1394 (7.75%)  115/1399 (8.22%)  53/527 (10.06%) 
General disorders       
Oedema peripheral  1  70/1394 (5.02%)  84/1399 (6.00%)  30/527 (5.69%) 
Infections and infestations       
Urinary tract infection  1  155/1394 (11.12%)  163/1399 (11.65%)  71/527 (13.47%) 
Upper respiratory tract infection  1  162/1394 (11.62%)  153/1399 (10.94%)  49/527 (9.30%) 
Nasopharyngitis  1  133/1394 (9.54%)  162/1399 (11.58%)  44/527 (8.35%) 
Influenza  1  113/1394 (8.11%)  132/1399 (9.44%)  42/527 (7.97%) 
Bronchitis  1  94/1394 (6.74%)  111/1399 (7.93%)  26/527 (4.93%) 
Pharyngitis  1  67/1394 (4.81%)  69/1399 (4.93%)  27/527 (5.12%) 
Sinusitis  1  70/1394 (5.02%)  64/1399 (4.57%)  23/527 (4.36%) 
Metabolism and nutrition disorders       
Dyslipidaemia  1  80/1394 (5.74%)  80/1399 (5.72%)  30/527 (5.69%) 
Hypertriglyceridaemia  1  54/1394 (3.87%)  62/1399 (4.43%)  28/527 (5.31%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  118/1394 (8.46%)  108/1399 (7.72%)  37/527 (7.02%) 
Back pain  1  102/1394 (7.32%)  111/1399 (7.93%)  46/527 (8.73%) 
Pain in extremity  1  67/1394 (4.81%)  80/1399 (5.72%)  32/527 (6.07%) 
Nervous system disorders       
Headache  1  90/1394 (6.46%)  105/1399 (7.51%)  40/527 (7.59%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  84/1394 (6.03%)  72/1399 (5.15%)  27/527 (5.12%) 
Vascular disorders       
Hypertension  1  207/1394 (14.85%)  203/1399 (14.51%)  85/527 (16.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
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.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00306384     History of Changes
Other Study ID Numbers: SYR-322-OLE-012
2005-004672-20 ( EudraCT Number )
U1111-1113-8455 ( Registry Identifier: WHO )
First Submitted: March 21, 2006
First Posted: March 23, 2006
Results First Submitted: February 17, 2013
Results First Posted: March 22, 2013
Last Update Posted: March 22, 2013