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

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT00306384
Collaborator
(none)
3,323
Enrollment
115
Locations
2
Arms
68
Duration (Months)
28.9
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term safety of alogliptin, once daily (QD), following participation in 1 of 7 controlled studies in patients with type 2 diabetes mellitus.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

SYR-322 (alogliptin) is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes mellitus by prolonging the beneficial effects of glucagon-like peptide-1.

The rising incidence of type 2 diabetes mellitus and the limitations of the currently available treatments suggest the need for new therapies for glycemic control. Studies have been undertaken in humans that evaluated the effects of directly augmenting glucagon-like peptide-1 and glucose-dependent insulinotropic peptide levels and of inhibiting the activity of dipeptidyl peptidase IV.

This study is an extension of 7 controlled phase 3 studies of alogliptin. These phase 3 studies included 1 monotherapy study of alogliptin (SYR-322-PLC-010; NCT00286455); 4 placebo-controlled add-on studies of alogliptin, namely in combination with a sulfonylurea (SYR-322-SULF-007; NCT00286468), metformin (SYR-322-MET-008; NCT00286442), a thiazolidinedione (pioglitazone; SYR-322-TZD-009; NCT00286494), and insulin (SYR-322-INS-011; NCT00286429); 1 coadministration study with pioglitazone in combination with metformin (01-05-TL-322OPI-001; NCT00328627), and 1 coadministration study with pioglitazone (01-06-TL-322OPI-002; NCT00395512).

The end of treatment or early withdrawal visit from the preceding study will be the screening visit for this study, after which enrolled patients will be required to commit to approximately 22 additional visits at the study center.

Study Design

Study Type:
Interventional
Actual Enrollment :
3323 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Long-Term, Open-Label Extension Study to Investigate the Long-Term Safety of SYR110322 (SYR-322) in Subjects With Type 2 Diabetes
Study Start Date :
Mar 1, 2006
Actual Primary Completion Date :
Nov 1, 2011
Actual Study Completion Date :
Nov 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alogliptin 12.5 mg

Alogliptin 12.5 tablet, orally, once daily for up to 4 years.

Drug: Alogliptin
Alogliptin tablets.
Other Names:
  • SYR110322
  • SYR-322

    		•
    Experimental: Alogliptin 25 mg

    Alogliptin 25 mg tablet, orally, once daily for up to 4 years.

    Drug: Alogliptin
    Alogliptin tablets.
    Other Names:
  • SYR110322
  • SYR-322

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [4 years]

      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.

    Secondary Outcome Measures

    1. Change From Baseline Over Time in Glycosylated Hemoglobin [Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45.]

      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.

    2. Change From Baseline in Fasting Plasma Glucose [Baseline and Year 4]

      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.

    3. Percentage of Participants With Marked Hyperglycemia [Randomization up to 4 years.]

      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).

    4. Change From Baseline in Proinsulin Level [Baseline and Year 4]

      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.

    5. Change From Baseline in Insulin Level [Baseline and Year 4]

      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.

    6. Change From Baseline in C-peptide Level [Baseline and Year 4]

      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.

    7. Change From Baseline in Body Weight [Baseline and Year 4]

      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.

    8. Percentage of Participants With a Clinical Response [Weeks 2, 4, 8, 12, every 3 months up to 4 years, and 1 Day after final dose.]

      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%.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

    • Type 2 diabetes mellitus and was enrolled in one of the following 7 controlled Phase III studies. The study will be open to all patients who completed one of these studies through the end-of-treatment visit:

    • 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

    • Alanine aminotransferase less than or equal to 3 times the upper limit of normal and serum creatinine less than or equal to 2.0 mg per dL.

    • Able and willing to monitor own blood glucose concentrations with a home glucose monitor.

    • No major illness or debility that in the investigator's opinion prohibits the patient from completing the study.

    Exclusion Criteria

    • The occurrence of any adverse event or condition during the controlled Phase III studies, which, in the opinion of the investigator, should exclude the patient from participating in the open-label extension.

    • Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • Weight-loss drugs

    • Investigational antidiabetics, additional dipeptidyl peptidase-4 (DPP-4) and glucagon-like peptide-1 (GLP 1) inhibitors

    • Incretin Mimetics,

    • Oral or systemically injected glucocorticoids.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States
    2 Peoria Arizona United States
    3 Phoenix Arizona United States
    4 Anaheim California United States
    5 Artesia California United States
    6 Fresno California United States
    7 Los Angeles California United States
    8 Mission Viejo California United States
    9 Northridge California United States
    10 Orange California United States
    11 San Diego California United States
    12 Tustin California United States
    13 Walnut Creek California United States
    14 Colorado Springs Colorado United States
    15 Denver Colorado United States
    16 Norwalk Connecticut United States
    17 Washington District of Columbia United States
    18 Clearwater Florida United States
    19 Hollywood Florida United States
    20 Kissimmee Florida United States
    21 Longwood Florida United States
    22 New Port Richie Florida United States
    23 Ocala Florida United States
    24 Ocoee Florida United States
    25 St. Cloud Florida United States
    26 Lawrenceville Georgia United States
    27 Honolulu Hawaii United States
    28 Idaho Falls Idaho United States
    29 Chicago Illinois United States
    30 Avon Indiana United States
    31 Elkhart Indiana United States
    32 Evansville Indiana United States
    33 Lafayette Indiana United States
    34 Erlanger Kentucky United States
    35 Baltimore Maryland United States
    36 Sudbury Massachusetts United States
    37 Chesterfield Missouri United States
    38 St. Louis Missouri United States
    39 Omaha Nebraska United States
    40 Berlin New Jersey United States
    41 Burlington North Carolina United States
    42 Charlotte North Carolina United States
    43 Morehead City North Carolina United States
    44 Pinehurst North Carolina United States
    45 Winston-Salem North Carolina United States
    46 Cincinnatti Ohio United States
    47 Dayton Ohio United States
    48 Tulsa Oklahoma United States
    49 Medford Oregon United States
    50 Lansdale Pennsylvania United States
    51 West Grove Pennsylvania United States
    52 Charleston South Carolina United States
    53 Columbia South Carolina United States
    54 Simpsonville South Carolina United States
    55 Bristol Tennessee United States
    56 Cookeville Tennessee United States
    57 Milan Tennessee United States
    58 Dallas Texas United States
    59 San Antonio Texas United States
    60 Temple Texas United States
    61 Texarkana Texas United States
    62 Burlington Vermont United States
    63 Buenos Aires La Plata Argentina
    64 Buenos Aires Moron Argentina
    65 Rosario Sante Fe Argentina
    66 Buenos Aires Argentina
    67 Ciudadd Autonoma de Buenos Aires Argentina
    68 Cordoba Argentina
    69 Mar del Plata Argentina
    70 Fortaleza Ceara Brazil
    71 Curitiba Parana Brazil
    72 Porto Alegre Rio Grande do Sul Brazil
    73 Mogi das Cruzes Sao Paulo Brazil
    74 Santos Sao Paulo Brazil
    75 Sao Paulo Brazil
    76 Santiago Chile
    77 Ostrava Czech Republic
    78 Prague Czech Republic
    79 Praha Czech Republic
    80 Sternberk Czech Republic
    81 Zlin Czech Republic
    82 Santo Domingo Oeste Dominican Republic
    83 Aschaffenburg Germany
    84 Berlin Germany
    85 Frankfurt Germany
    86 Hamburg Germany
    87 Hannover Germany
    88 Munich Germany
    89 Nuremberg Germany
    90 Schwerin Germany
    91 Wiesbaden Germany
    92 Witten Germany
    93 Guatemala Guatemala
    94 Almere Netherlands
    95 De Bilt Netherlands
    96 Geleen Netherlands
    97 Oud-Beijerland Netherlands
    98 Rotterdam Netherlands
    99 Zwijndrecht Netherlands
    100 Bellavista Lima Peru
    101 San Isidro Lima Peru
    102 Ica Peru
    103 Lima Peru
    104 Bytom Poland
    105 Kamieniec Zabkowicki Poland
    106 Krakow Poland
    107 Leczyca Poland
    108 Lodz Poland
    109 Radom Poland
    110 Pretoria Gauteng South Africa
    111 Cape Town Western Cape South Africa
    112 Somerset West Western Cape South Africa
    113 Durban South Africa
    114 Johannesburg South Africa
    115 Parow South Africa

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: VP Biological Sciences, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT00306384
    Other Study ID Numbers:
    • SYR-322-OLE-012
    • 2005-004672-20
    • U1111-1113-8455
    First Posted:
    Mar 23, 2006
    Last Update Posted:
    Mar 22, 2013
    Last Verified:
    Feb 1, 2013
    Keywords provided by Takeda
    Glucose Metabolism Disorder
    Dysmetabolic Syndrome
    Type II Diabetes
    Diabetes Mellitus,
    Lipoatrophic
    Dyslipidemia
    Drug Therapy
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Alogliptin

    Study Results

    Participant Flow

    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 Detail 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
    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 1398 527
    COMPLETED 854 891 251
    NOT COMPLETED 542 508 277

    Baseline Characteristics

    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg Total
    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 Participants 1396 1399 528 3323
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.8
    (9.92)
    55.1
    (10.21)
    53.0
    (10.06)
    55.0
    (10.11)
    Age, Customized (participants) [Number]
    <65 years
    1134
    81.2%
    1134
    81.1%
    461
    87.3%
    2729
    82.1%
    ≥65 years
    262
    18.8%
    265
    18.9%
    67
    12.7%
    594
    17.9%
    Sex: Female, Male (Count of 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 (participants) [Number]
    American Indian or Alaska Native
    8
    0.6%
    3
    0.2%
    2
    0.4%
    13
    0.4%
    Asian
    120
    8.6%
    108
    7.7%
    32
    6.1%
    260
    7.8%
    Native Hawaiian or Other Pacific Islander
    2
    0.1%
    0
    0%
    1
    0.2%
    3
    0.1%
    Black or African American
    65
    4.7%
    88
    6.3%
    34
    6.4%
    187
    5.6%
    White
    1025
    73.4%
    1007
    72%
    390
    73.9%
    2422
    72.9%
    Other
    176
    12.6%
    193
    13.8%
    69
    13.1%
    438
    13.2%
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    31.42
    (5.370)
    31.71
    (5.266)
    32.20
    (5.704)
    31.66
    (5.386)
    Diabetes duration (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    6.56
    (5.446)
    6.92
    (5.824)
    8.35
    (6.325)
    6.99
    (5.784)
    Previous double-blind study treatment (participants) [Number]
    Placebo
    118
    8.5%
    110
    7.9%
    135
    25.6%
    363
    10.9%
    Alogliptin 12.5 mg
    274
    19.6%
    262
    18.7%
    105
    19.9%
    641
    19.3%
    Alogliptin 25 mg
    243
    17.4%
    262
    18.7%
    99
    18.8%
    604
    18.2%
    Study 01-05-TL-322OPI-001
    546
    39.1%
    548
    39.2%
    146
    27.7%
    1240
    37.3%
    Study 01-06-TL-322OPI-002
    215
    15.4%
    217
    15.5%
    43
    8.1%
    475
    14.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
    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

    Outcome Measure Data

    Analysis Population Description
    Safety set
    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    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.
    Measure Participants 1394 1399 527
    Any treatment emergent adverse event (TEAE)
    87.2
    6.2%
    87.1
    6.2%
    84.6
    16%
    Study drug-related TEAE
    25.6
    1.8%
    22.7
    1.6%
    24.9
    4.7%
    TEAE leading to discontinuation
    7.0
    0.5%
    6.1
    0.4%
    7.6
    1.4%
    Treatment emergent serious AE
    16.7
    1.2%
    16.3
    1.2%
    15.7
    3%
    Study drug-related serious AE
    2.6
    0.2%
    2.1
    0.2%
    1.9
    0.4%
    Treatment-emergent deaths
    1.4
    0.1%
    1.0
    0.1%
    0.9
    0.2%
    2. Secondary Outcome
    Title Change From Baseline Over Time in Glycosylated Hemoglobin
    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.

    Outcome Measure Data

    Analysis Population Description
    Safety set where data were available.
    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    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.
    Measure Participants 1395 1398 527
    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
    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

    Outcome Measure Data

    Analysis Population Description
    Safety set where data were available.
    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    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.
    Measure Participants 1388 1386 517
    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
    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.

    Outcome Measure Data

    Analysis Population Description
    Safety set where data were available.
    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    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.
    Measure Participants 1395 1398 527
    Day 1 to <Week 2 (n=1299, 1290, 481)
    9.1
    0.7%
    8.0
    0.6%
    55.5
    10.5%
    Week 2 to <Week 4 (n=1286, 1306, 481)
    11.5
    0.8%
    10.2
    0.7%
    45.9
    8.7%
    Week 4 to <Week 8 (n=1303, 1331, 490)
    9.2
    0.7%
    11.0
    0.8%
    46.1
    8.7%
    Week 8 to <Week 12 (n=1331, 1347, 495)
    11.5
    0.8%
    10.8
    0.8%
    41.0
    7.8%
    Week 12 to <Month 6 (n=1329, 1338, 480)
    12.0
    0.9%
    11.6
    0.8%
    39.4
    7.5%
    Month 6 to <Month 9 (n=1286, 1289, 448)
    12.8
    0.9%
    10.7
    0.8%
    36.8
    7%
    Month 9 to <Month 12 (n=1252, 1260, 425)
    11.4
    0.8%
    12.9
    0.9%
    32.5
    6.2%
    Month 12 to <Month 15 (n=1210, 1217, 409)
    13.1
    0.9%
    13.0
    0.9%
    29.3
    5.5%
    Month 15 to <Month 18 (n=1157, 1166, 389)
    12.7
    0.9%
    13.8
    1%
    27.8
    5.3%
    Month 18 to <Month 21 (n=1128, 1128, 365)
    11.7
    0.8%
    11.6
    0.8%
    26.8
    5.1%
    Month 21 to <Month 24 (n=1094,1099, 357)
    11.2
    0.8%
    11.5
    0.8%
    26.3
    5%
    Month 24 to <Month 27 (n=1046, 1066, 334)
    11.6
    0.8%
    12.3
    0.9%
    24.9
    4.7%
    Month 27 to <Month 30 (n=1010, 1028, 316)
    12.6
    0.9%
    11.8
    0.8%
    24.7
    4.7%
    Month 30 to <Month 33 (n=981, 988, 299)
    11.6
    0.8%
    11.7
    0.8%
    19.7
    3.7%
    Month 33 to <Month 36 (n=945, 959, 289)
    11.5
    0.8%
    12.3
    0.9%
    23.5
    4.5%
    Month 36 to <Month 39 (n=920, 949, 281)
    13.2
    0.9%
    12.5
    0.9%
    21.0
    4%
    Month 39 to <Month 42 (n=899, 934, 267)
    13.7
    1%
    13.1
    0.9%
    19.5
    3.7%
    Month 42 to Month 45 (n=889, 921, 261)
    25.5
    1.8%
    23.9
    1.7%
    39.1
    7.4%
    Overall (n= 1389, 1392, 518)
    49.7
    3.6%
    50.7
    3.6%
    87.6
    16.6%
    5. Secondary Outcome
    Title Change From Baseline in Proinsulin Level
    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

    Outcome Measure Data

    Analysis Population Description
    Safety set where data were available.
    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    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.
    Measure Participants 1277 1263 393
    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
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 537 526 212
    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
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 615 615 322
    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
    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

    Outcome Measure Data

    Analysis Population Description
    Safety set for whom data was available.
    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    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.
    Measure Participants 1387 1385 518
    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
    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.

    Outcome Measure Data

    Analysis Population Description
    Safety set.
    Arm/Group Title Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    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.
    Measure Participants 1395 1398 527
    HbA1c ≤6.5%
    34.8
    2.5%
    34.1
    2.4%
    11.0
    2.1%
    HbA1c ≤7.0%
    64.1
    4.6%
    65.5
    4.7%
    27.1
    5.1%

    Adverse Events

    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
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 233/1394 (16.7%) 228/1399 (16.3%) 83/527 (15.7%)
    Blood and lymphatic system disorders
    Anaemia 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Iron deficiency anaemia 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Cardiac disorders
    Acute myocardial infarction 7/1394 (0.5%) 11/1399 (0.8%) 4/527 (0.8%)
    Coronary artery disease 5/1394 (0.4%) 7/1399 (0.5%) 5/527 (0.9%)
    Myocardial infarction 5/1394 (0.4%) 6/1399 (0.4%) 4/527 (0.8%)
    Angina pectoris 5/1394 (0.4%) 5/1399 (0.4%) 2/527 (0.4%)
    Angina unstable 6/1394 (0.4%) 3/1399 (0.2%) 2/527 (0.4%)
    Myocardial ischaemia 7/1394 (0.5%) 3/1399 (0.2%) 0/527 (0%)
    Atrial fibrillation 1/1394 (0.1%) 4/1399 (0.3%) 1/527 (0.2%)
    Acute coronary syndrome 2/1394 (0.1%) 1/1399 (0.1%) 2/527 (0.4%)
    Cardiac failure congestive 0/1394 (0%) 2/1399 (0.1%) 2/527 (0.4%)
    Ischaemic cardiomyopathy 1/1394 (0.1%) 2/1399 (0.1%) 1/527 (0.2%)
    Cardiac failure 1/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Cardio-respiratory arrest 1/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Atrioventricular block complete 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Atrioventricular block second degree 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Coronary artery stenosis 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Pericardial effusion 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Tachycardia 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Ventricular extrasystoles 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Aortic valve stenosis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Arteriosclerosis coronary artery 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Bradycardia 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Cardiomyopathy 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Cardiopulmonary failure 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Congestive cardiomyopathy 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Coronary artery insufficiency 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Hypertensive heart disease 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Left ventricular dysfunction 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Palpitations 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pericarditis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Sick sinus syndrome 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Congenital, familial and genetic disorders
    MELAS syndrome 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Endocrine disorders
    Goitre 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Hyperthyroidism 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Eye disorders
    Cataract 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Retinal vein thrombosis 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Diabetic retinopathy 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Glaucoma 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Iridocyclitis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Retinal artery occlusion 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Retinal detachment 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Vitreous haemorrhage 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Gastrointestinal disorders
    Pancreatitis 1/1394 (0.1%) 4/1399 (0.3%) 1/527 (0.2%)
    Inguinal hernia 3/1394 (0.2%) 0/1399 (0%) 1/527 (0.2%)
    Abdominal pain 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Diarrhoea 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Gastric ulcer haemorrhage 1/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Pancreatitis acute 3/1394 (0.2%) 0/1399 (0%) 0/527 (0%)
    Gastric ulcer 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Gastritis 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Gastrointestinal haemorrhage 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Umbilical hernia 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Abdominal hernia 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Abdominal pain upper 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Anal fistula 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Colitis ischaemic 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Diverticulum intestinal haemorrhagic 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Duodenal ulcer 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Duodenal ulcer haemorrhage 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Dyspepsia 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Gastrointestinal hypomotility 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Gastrointestinal necrosis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Haematemesis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Haemorrhoids 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Hernial eventration 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Intestinal obstruction 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Intra-abdominal haemorrhage 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pancreatitis relapsing 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Peptic ulcer 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Peritonitis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Rectal polyp 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Rectal prolapse 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Salivary duct inflammation 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Small intestinal obstruction 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    General disorders
    Non-cardiac chest pain 4/1394 (0.3%) 4/1399 (0.3%) 2/527 (0.4%)
    Chest pain 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Pyrexia 0/1394 (0%) 0/1399 (0%) 2/527 (0.4%)
    Death 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Influenza like illness 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Hepatobiliary disorders
    Cholelithiasis 3/1394 (0.2%) 4/1399 (0.3%) 2/527 (0.4%)
    Cholecystitis acute 4/1394 (0.3%) 2/1399 (0.1%) 1/527 (0.2%)
    Cholecystitis 1/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Bile duct stone 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Biliary colic 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Cholangitis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Hepatitis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Perforation bile duct 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Immune system disorders
    Allergic oedema 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Allergy to arthropod sting 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Infections and infestations
    Pneumonia 13/1394 (0.9%) 6/1399 (0.4%) 0/527 (0%)
    Cellulitis 4/1394 (0.3%) 3/1399 (0.2%) 4/527 (0.8%)
    Urinary tract infection 5/1394 (0.4%) 4/1399 (0.3%) 0/527 (0%)
    Erysipelas 2/1394 (0.1%) 3/1399 (0.2%) 0/527 (0%)
    Osteomyelitis 3/1394 (0.2%) 1/1399 (0.1%) 1/527 (0.2%)
    Diverticulitis 2/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Gastroenteritis 1/1394 (0.1%) 2/1399 (0.1%) 1/527 (0.2%)
    Gangrene 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Postoperative wound infection 1/1394 (0.1%) 1/1399 (0.1%) 1/527 (0.2%)
    Abscess limb 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Appendicitis 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Bronchitis 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Bronchopneumonia 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Dengue fever 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Diabetic foot infection 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Infected skin ulcer 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Lobar pneumonia 0/1394 (0%) 0/1399 (0%) 2/527 (0.4%)
    Lower respiratory tract infection 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Post procedural infection 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Pyelonephritis 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Staphylococcal infection 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Viral infection 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Acquired immunodeficiency syndrome 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Appendicitis perforated 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Arthritis bacterial 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Cholecystitis infective 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Coccidioidomycosis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Endophthalmitis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Gastroenteritis viral 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Giardiasis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Helicobacter gastritis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Hepatitis A 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Herpes zoster 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Labyrinthitis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lymphangitis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Nosocomial infection 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Peritonsillar abscess 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Pneumococcal sepsis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pneumonia cryptococcal 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pneumonia pneumococcal 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pulmonary tuberculosis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Pyelonephritis acute 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pyelonephritis chronic 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Pyoderma 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Rectal abscess 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Septic shock 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Sialoadenitis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Subcutaneous abscess 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Tooth abscess 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Typhoid fever 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Urosepsis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Wound infection 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Wound sepsis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Injury, poisoning and procedural complications
    Fall 3/1394 (0.2%) 1/1399 (0.1%) 1/527 (0.2%)
    Hip fracture 1/1394 (0.1%) 3/1399 (0.2%) 0/527 (0%)
    Head injury 0/1394 (0%) 3/1399 (0.2%) 0/527 (0%)
    Subdural haematoma 2/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Ankle fracture 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Clavicle fracture 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Femur fracture 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Humerus fracture 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Incisional hernia 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Multiple fractures 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Patella fracture 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Rib fracture 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Tendon injury 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Tendon rupture 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Tibia fracture 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Anaemia postoperative 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Chest injury 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Device occlusion 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Femoral neck fracture 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Foreign body trauma 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Hand fracture 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Incisional hernia, obstructive 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Laceration 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lower limb fracture 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lumbar vertebral fracture 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Multiple injuries 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Post procedural complication 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Radius fracture 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Road traffic accident 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Thermal burn 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Traumatic fracture 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Metabolism and nutrition disorders
    Hyperglycaemia 1/1394 (0.1%) 3/1399 (0.2%) 3/527 (0.6%)
    Diabetic foot 1/1394 (0.1%) 3/1399 (0.2%) 0/527 (0%)
    Dehydration 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Hyperkalaemia 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Hypertriglyceridaemia 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Hyponatraemia 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Obesity 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Hypoglycaemic seizure 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 3/1394 (0.2%) 6/1399 (0.4%) 1/527 (0.2%)
    Rotator cuff syndrome 1/1394 (0.1%) 6/1399 (0.4%) 1/527 (0.2%)
    Intervertebral disc protrusion 3/1394 (0.2%) 3/1399 (0.2%) 0/527 (0%)
    Musculoskeletal chest pain 2/1394 (0.1%) 3/1399 (0.2%) 0/527 (0%)
    Arthralgia 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Back pain 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Arthritis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Chondromalacia 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Intervertebral disc degeneration 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Intervertebral disc disorder 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lumbar spinal stenosis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Muscle disorder 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Muscular weakness 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Myopathy 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Osteochondrosis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Rhabdomyolysis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Spondylolisthesis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Synovitis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Tendon calcification 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 2/1394 (0.1%) 3/1399 (0.2%) 2/527 (0.4%)
    Uterine leiomyoma 1/1394 (0.1%) 3/1399 (0.2%) 0/527 (0%)
    Basal cell carcinoma 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Breast cancer female 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Meningioma 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Prostate cancer 2/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Rectal cancer 1/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Brain neoplasm 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Lung neoplasm 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Lung neoplasm malignant 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Ovarian adenoma 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Pancreatic carcinoma 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Thyroid cancer 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Acute leukaemia 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Adrenal adenoma 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    B-cell lymphoma 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Benign neoplasm of adrenal gland 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Bladder transitional cell carcinoma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Brain neoplasm benign 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Breast cancer stage I 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Breast cancer stage III 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Carcinoid tumour of the appendix 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Central nervous system neoplasm 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Cervix carcinoma stage 0 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Cervix neoplasm 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Choroid melanoma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Chronic lymphocytic leukaemia 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Colon cancer 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Colon cancer stage III 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Colorectal cancer 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Focal nodular hyperplasia 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Gastrointestinal stromal tumour 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Haemangioma of liver 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Hepatic neoplasm malignant 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Langerhans' cell granulomatosis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lung adenocarcinoma 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lung cancer metastatic 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Malignant melanoma in situ 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Mantle cell lymphoma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Mesothelioma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Metastases to liver 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Metastases to peritoneum 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Multiple myeloma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Neuroendocrine tumour 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Non-Hodgkin's lymphoma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Non-small cell lung cancer metastatic 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Oesophageal adenocarcinoma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Oligodendroglioma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Ovarian cancer 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Ovarian germ cell teratoma benign 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Prostatic adenom 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Renal cell carcinoma 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Renal neoplasm 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Squamous cell carcinoma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Thyroid neoplasm 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Transitional cell carcinoma 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Nervous system disorders
    Cerebrovascular accident 6/1394 (0.4%) 1/1399 (0.1%) 4/527 (0.8%)
    Ischaemic stroke 6/1394 (0.4%) 1/1399 (0.1%) 1/527 (0.2%)
    Syncope 4/1394 (0.3%) 1/1399 (0.1%) 0/527 (0%)
    Carotid artery stenosis 0/1394 (0%) 3/1399 (0.2%) 0/527 (0%)
    Convulsion 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Loss of consciousness 3/1394 (0.2%) 0/1399 (0%) 0/527 (0%)
    Transient ischaemic attack 2/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Cerebral ischaemia 0/1394 (0%) 1/1399 (0.1%) 1/527 (0.2%)
    Dizziness 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Haemorrhage intracranial 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Altered state of consciousness 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Amnesia 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Brain stem syndrome 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Carpal tunnel syndrome 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Cerebral artery occlusion 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Diabetic mononeuropathy 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Diabetic neuropathy 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Dysarthria 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Embolic stroke 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Facial palsy 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Grand mal convulsion 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Haemorrhagic stroke 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Hydrocephalus 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lacunar infarction 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Normal pressure hydrocephalus 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Presyncope 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Radial nerve palsy 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Reversible ischaemic neurological deficit 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Subarachnoid haemorrhage 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Vascular headache 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous incomplete 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Ectopic pregnancy 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Psychiatric disorders
    Major depression 0/1394 (0%) 2/1399 (0.1%) 0/527 (0%)
    Anxiety 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Anxiety disorder 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Hypnagogic hallucination 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Mental disorder 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Panic attack 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Suicide attempt 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Renal and urinary disorders
    Renal failure acute 2/1394 (0.1%) 7/1399 (0.5%) 1/527 (0.2%)
    Nephrolithiasis 2/1394 (0.1%) 5/1399 (0.4%) 1/527 (0.2%)
    Calculus ureteric 3/1394 (0.2%) 1/1399 (0.1%) 1/527 (0.2%)
    Renal colic 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Haematuria 1/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Calculus urethral 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Diabetic nephropathy 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Postrenal failure 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Renal failure 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Renal failure chronic 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Stress urinary incontinence 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Tubulointerstitial nephritis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Urinary retention 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Reproductive system and breast disorders
    Menorrhagia 0/1394 (0%) 3/1399 (0.2%) 1/527 (0.2%)
    Ovarian cyst 1/1394 (0.1%) 3/1399 (0.2%) 0/527 (0%)
    Benign prostatic hyperplasia 1/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Colpocele 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Endometrial hyperplasia 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Genital prolapse 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Breast calcifications 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Epididymal cyst 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Erectile dysfunction 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Fallopian tube cyst 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Menometrorrhagia 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Metrorrhagia 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Pelvic pain 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Uterine polyp 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Uterine prolapse 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Vocal cord polyp 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 2/1394 (0.1%) 2/1399 (0.1%) 0/527 (0%)
    Acute pulmonary oedema 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Asthma 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Dyspnoea 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Pleural effusion 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pulmonary oedema 1/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Acute respiratory failure 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Asphyxia 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Asthmatic crisis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Epistaxis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Lung disorder 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pleurisy 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pneumonia aspiration 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Pulmonary embolism 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Pulmonary hypertension 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Respiratory failure 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Sleep apnoea syndrome 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Skin and subcutaneous tissue disorders
    Angioedema 1/1394 (0.1%) 1/1399 (0.1%) 1/527 (0.2%)
    Skin ulcer 2/1394 (0.1%) 0/1399 (0%) 1/527 (0.2%)
    Dermatitis allergic 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Drug eruption 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Rash 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Skin necrosis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Urticaria 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Surgical and medical procedures
    Knee arthroplasty 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Vascular disorders
    Deep vein thrombosis 2/1394 (0.1%) 1/1399 (0.1%) 0/527 (0%)
    Peripheral vascular disorder 1/1394 (0.1%) 1/1399 (0.1%) 1/527 (0.2%)
    Hypertension 2/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Arteriosclerosis 0/1394 (0%) 1/1399 (0.1%) 0/527 (0%)
    Hypertensive crisis 1/1394 (0.1%) 0/1399 (0%) 0/527 (0%)
    Pelvic venous thrombosis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Venous thrombosis 0/1394 (0%) 0/1399 (0%) 1/527 (0.2%)
    Other (Not Including Serious) Adverse Events
    Alogliptin 12.5 mg Alogliptin 25 mg Rescued: Alogliptin 25 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 876/1394 (62.8%) 898/1399 (64.2%) 333/527 (63.2%)
    Gastrointestinal disorders
    Diarrhoea 108/1394 (7.7%) 115/1399 (8.2%) 53/527 (10.1%)
    General disorders
    Oedema peripheral 70/1394 (5%) 84/1399 (6%) 30/527 (5.7%)
    Infections and infestations
    Urinary tract infection 155/1394 (11.1%) 163/1399 (11.7%) 71/527 (13.5%)
    Upper respiratory tract infection 162/1394 (11.6%) 153/1399 (10.9%) 49/527 (9.3%)
    Nasopharyngitis 133/1394 (9.5%) 162/1399 (11.6%) 44/527 (8.3%)
    Influenza 113/1394 (8.1%) 132/1399 (9.4%) 42/527 (8%)
    Bronchitis 94/1394 (6.7%) 111/1399 (7.9%) 26/527 (4.9%)
    Pharyngitis 67/1394 (4.8%) 69/1399 (4.9%) 27/527 (5.1%)
    Sinusitis 70/1394 (5%) 64/1399 (4.6%) 23/527 (4.4%)
    Metabolism and nutrition disorders
    Dyslipidaemia 80/1394 (5.7%) 80/1399 (5.7%) 30/527 (5.7%)
    Hypertriglyceridaemia 54/1394 (3.9%) 62/1399 (4.4%) 28/527 (5.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 118/1394 (8.5%) 108/1399 (7.7%) 37/527 (7%)
    Back pain 102/1394 (7.3%) 111/1399 (7.9%) 46/527 (8.7%)
    Pain in extremity 67/1394 (4.8%) 80/1399 (5.7%) 32/527 (6.1%)
    Nervous system disorders
    Headache 90/1394 (6.5%) 105/1399 (7.5%) 40/527 (7.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 84/1394 (6%) 72/1399 (5.1%) 27/527 (5.1%)
    Vascular disorders
    Hypertension 207/1394 (14.8%) 203/1399 (14.5%) 85/527 (16.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    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
    Email clinicaltrialregistry@tpna.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT00306384
    Other Study ID Numbers:
    • SYR-322-OLE-012
    • 2005-004672-20
    • U1111-1113-8455
    First Posted:
    Mar 23, 2006
    Last Update Posted:
    Mar 22, 2013
    Last Verified:
    Feb 1, 2013