Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7293   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Alogliptin Compared With Placebo in Pediatric Subjects With Type 2 Diabetes Mellitus

    Summary
    EudraCT number
    		 2015-000208-25
    Trial protocol
    		 IT   PL   Outside EU/EEA  
    Global end of trial date
    13 Feb 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    01 Sep 2022
    First version publication date
    14 Aug 2022
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Update to question "Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?", it should be Yes.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SYR-322_309
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02856113
    WHO universal trial number (UTN)
    		 U1111-1174-1923
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Avenue, Lexington, United States, MA 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000496-PIP01-08
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    06 Aug 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Aug 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to evaluate the efficacy of alogliptin 25 mg once daily compared to placebo when administered as monotherapy, or when added onto a background of metformin alone, insulin alone, or a combination of metformin and insulin, as measured by the glycosylated hemoglobin (HbA1c) change from Baseline at Week 26 in pediatric participants with type 2 diabetes mellitus (T2DM).
    Protection of trial subjects
    Study participants were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Oct 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 1
    Country: Number of subjects enrolled
    Israel: 1
    Country: Number of subjects enrolled
    Mexico: 73
    Country: Number of subjects enrolled
    United States: 72
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Russian Federation: 3
    Worldwide total number of subjects
    151
    EEA total number of subjects
    1
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    18
    Adolescents (12-17 years)
    133
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 152 participants took part in the study at 67 investigative sites in Mexico, United States, Brazil, Israel, Italy and Russia from 14 October 2016 to 14 February 2022.

    Pre-assignment
    Screening details
    		 Participants with type 2 diabetes mellitus were enrolled to receive placebo or alogliptin 25 mg in a 1:1 ratio in this study.

    Pre-assignment period milestones
    Number of subjects started
    		 77 [1]
    Number of subjects completed
    		 76

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Randomized but not Treated: 1
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: There was 1 participant who was randomized but not treated.
    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo
    Arm description
    		 Alogliptin matching-placebo tablets, orally, once daily (QD) for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Alogliptin matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Alogliptin matching placebo tablets

    Arm title
    		 Alogliptin 25 mg
    Arm description
    		 Alogliptin 25 mg tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Alogliptin 25 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Alogliptin matching placebo tablets

    Number of subjects in period 1
    		Placebo Alogliptin 25 mg
    Started
    76
    75
    Safety Population
    76
    75
    Completed
    66
    60
    Not completed
    10
    15
         Pretreatment Event/Adverse Event
    1
    -
         Voluntary Withdrawal
    3
    5
         Significant Protocol Deviation
    1
    -
         Pregnancy
    -
    1
         Principal Investigator Discretion
    2
    1
         Did not Complete Study but Contacted at Week 52
    -
    3
         Lost to follow-up
    3
    5

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Alogliptin matching-placebo tablets, orally, once daily (QD) for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.

    Reporting group title
    Alogliptin 25 mg
    Reporting group description
    		 Alogliptin 25 mg tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.

    Reporting group values
    		 Placebo Alogliptin 25 mg Total
    Number of subjects
    		 76 75
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 14.3 ± 2.21 14.2 ± 1.92 -
    Gender categorical
    Units: Subjects
        Female
    		 51 53 104
        Male
    		 25 22 47
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 6 9 15
        Not Hispanic or Latino
    		 31 26 57
        Unknown or Not Reported
    		 39 40 79
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 14 11 25
        Asian
    		 1 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 16 16 32
        White
    		 44 44 88
        More than one race
    		 1 4 5
        Unknown or Not Reported
    		 0 0 0
    Height
    Units: centimetres (cm)
        arithmetic mean (standard deviation)
    		 164.7 ± 9.54 163.1 ± 8.79 -
    Weight
    Units: kilograms (kg)
        arithmetic mean (standard deviation)
    		 92.23 ± 26.826 90.72 ± 28.815 -
    Body Mass Index (BMI)
    BMI was calculated as weight (kg) divided by square of height (m^2).
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 33.632 ± 7.8581 33.669 ± 8.6592 -
    Baseline of Glycosylated Hemoglobin (HbA1c)
    HbA1c is defined as the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound.
    Units: percentage of HbA1c
        arithmetic mean (full range (min-max))
    		 8.11 (5.7 to 11.3) 8.16 (6.3 to 11.5) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Alogliptin matching-placebo tablets, orally, once daily (QD) for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.

    Reporting group title
    Alogliptin 25 mg
    Reporting group description
    		 Alogliptin 25 mg tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.

    Primary: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26

    		 Close Top of page
    End point title
    		 Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
    End point description
    Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Week 26 relative to Baseline. Mixed model for repeated measures (MMRM) was used for the analysis.
    End point type
    Primary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    56
    54
    Units: percentage of HbA1c
        least squares mean (standard deviation)
    -0.011 ± 0.2809
    0.091 ± 0.2879
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Alogliptin 25 mg v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.782 [1]
    Method
    		 MMRM
    Parameter type
    		 Least Square (LS) Mean Difference
    Point estimate
    0.102
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.627
         upper limit
    		 0.831
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3677
    Notes
    [1] - P-values was assessed at 0.05 significance level using MMRM.

    Secondary: Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52

    		 Close Top of page
    End point title
    		 Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52
    End point description
    Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Weeks 12, 18, 39 and 52 relative to Baseline. MMRM was used for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 12, 18, 39 and 52
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    62
    62
    Units: percentage of HbA1c
    least squares mean (standard deviation)
        Change From Baseline to Week 12
    -0.319 ± 0.2173
    -0.365 ± 0.2223
        Change From Baseline to Week 18
    -0.206 ± 0.2458
    -0.202 ± 0.2529
        Change From Baseline to Week 39
    0.502 ± 0.2802
    0.091 ± 0.2866
        Change From Baseline to Week 52
    0.764 ± 0.3118
    0.281 ± 0.3199
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Change From Baseline at Week 12
    Comparison groups
    Placebo v Alogliptin 25 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.863 [2]
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.046
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.567
         upper limit
    		 0.476
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2635
    Notes
    [2] - P-values was assessed at 0.05 significance level using MMRM.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Change From Baseline at Week 18
    Comparison groups
    Placebo v Alogliptin 25 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.99 [3]
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.004
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.614
         upper limit
    		 0.622
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3123
    Notes
    [3] - P-values was assessed at 0.05 significance level using MMRM.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Change From Baseline at Week 39
    Comparison groups
    Placebo v Alogliptin 25 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.264 [4]
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.412
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.139
         upper limit
    		 0.316
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3664
    Notes
    [4] - P-values was assessed at 0.05 significance level using MMRM.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Change From Baseline at Week 52
    Comparison groups
    Placebo v Alogliptin 25 mg
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.25 [5]
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.483
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.314
         upper limit
    		 0.348
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4165
    Notes
    [5] - P-values was assessed at 0.05 significance level using MMRM.

    Secondary: Percentage of Participants with Clinically Significant Physical Examination Findings

    		 Close Top of page
    End point title
    		 Percentage of Participants with Clinically Significant Physical Examination Findings
    End point description
    Physical examination included examination of the following body systems: (1) respiratory system; (2) cardiovascular system; (3) nervous system (4) dermatologic system; and (5) gastrointestinal system. A summarized data for the above body systems was reported for participants with clinically significant findings.
    End point type
    Secondary
    End point timeframe
    From Day 1 to end of treatment period (up to 52 weeks)
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    71
    71
    Units: percentage of participants
    number (not applicable)
        Week 4(n=1,0)
    0
    0
        Week 12(n=71,71)
    0
    0
        Week 18(n=2,1)
    0
    0
        Week 26(n=69,68)
    0
    0
        Week 32(n=3,0)
    0
    0
        Week 39(n=66,67)
    0
    0
        Week 45(n=2,0)
    0
    0
        Week 52(n=57,50)
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Abnormal Vital Signs Values

    		 Close Top of page
    End point title
    		 Percentage of Participants With Abnormal Vital Signs Values
    End point description
    Vital signs included body temperature (oral or tympanic measurement), respiratory rate, blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] resting more than 5 minutes, and pulse (beats per minute). Data for participants with abnormal vital signs was reported.
    End point type
    Secondary
    End point timeframe
    From Day 1 to end of treatment period (up to 52 weeks)
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    76
    75
    Units: percentage of participants
    number (not applicable)
        SBP (millimeters of mercury [mmHg]): >150
    1.3
    2.8
        DBP (mmHg): >95
    4.0
    4.2
        Pulse Rate (beats per minute [bpm]): <50
    0
    1.4
        Pulse Rate (bpm): >120
    0
    1.4
        Temperature (Celsius [C]): <35.6
    0
    3.1
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Abnormal 12-lead Electrocardiogram (ECG) Findings

    		Close Top of page
    End point title
    		 Percentage of Participants with Abnormal 12-lead Electrocardiogram (ECG) Findings
    End point description
    End point type
    Secondary
    End point timeframe
    Week 26 and 52
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    76
    75
    Units: participants
    number (not applicable)
        Week 26: Abnormal, Not Clinically Significant
    7
    6
        Week 26: Abnormal, Clinically Significant
    2
    0
        Week 52: Abnormal, Not Clinically Significant
    7
    6
        Week 52: Abnormal, Clinically Significant
    1
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Treatment-emergent Adverse Events (TEAE)

    		Close Top of page
    End point title
    		 Percentage of Participants with Treatment-emergent Adverse Events (TEAE)
    End point description
    An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
    End point type
    Secondary
    End point timeframe
    From the study start up to end of the study (up to 54 weeks)
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    76
    75
    Units: percentage of participants
        number (not applicable)
    76.3
    80.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions

    		Close Top of page
    End point title
    		 Percentage of Participants with Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions
    End point description
    End point type
    Secondary
    End point timeframe
    From Day 1 to end of treatment period (up to 52 weeks)
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    76
    75
    Units: percentage of participants
    number (not applicable)
        Bladder Infection
    0.0
    11.1
        COVID-19 Infection
    9.1
    0.0
        Low Urinary Tract Infection
    0.0
    11.1
        Respiratory Tract Infection
    9.1
    11.1
        Sinus Infection
    9.1
    11.1
        Upper Respiratory Infection
    18.2
    44.4
        Upper Respiratory Tract Infection
    9.1
    0.0
        Urinary Tract Infection
    9.1
    0.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Hypoglycemia

    		 Close Top of page
    End point title
    		 Percentage of Participants with Hypoglycemia
    End point description
    Mild to moderate hypoglycemia (abnormal low blood sugar) was defined as blood glucose less than (<) 60 milligram per deciliter (mg/dL) (3.33 millimole per liter [mmol/L]) in the presence of symptoms, or blood glucose <50 mg/dL (2.78 mmol/L) with or without symptoms. Severe hypoglycemia was defined as any episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, associated with a documented blood glucose <60 mg/dL (3.33 mmol/L) (unless the clinical situation makes obtaining a blood glucose difficult [example, it involves coma or seizure]).
    End point type
    Secondary
    End point timeframe
    From Day 1 to end of treatment period (up to 52 weeks)
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    76
    75
    Units: percentage of participants
        number (not applicable)
    7.9
    5.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Abnormal Safety Laboratory Findings

    		Close Top of page
    End point title
    		 Percentage of Participants with Abnormal Safety Laboratory Findings
    End point description
    The percentage of participants with any abnormal standard safety laboratory values (hematology, serum chemistry, and urinalysis) were collected throughout study. Abnormal values for hematology included hematocrit (percentage of hematocrit [%]), hemoglobin (grams per liter [g/L]), erythrocyte mean corpuscular volume (MCV)(femtoliter [fL]), erythrocytes (10^12/L), and leukocytes (10^9/L). Abnormal values for serum chemistry included for alanine aminotransferase (units per liter [U/L]), aspartate aminotransferase (U/L), cholesterol (millimoles per liter [mmol/L]), gamma glutamyl transferase (U/L), glucose (mmol/L): < 2.8 mmol/L, potassium (mmol/L), sodium (mmol/L), and triglycerides (mmol/L). ULN is upper limit of normal and LLN is lower limit of normal.
    End point type
    Secondary
    End point timeframe
    From Day 1 to end of treatment period (up to 52 weeks)
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    75
    73
    Units: percentage of participants
    number (not applicable)
        Alanine Aminotransferase (U/L): ≥3xULN(n=75,72)
    10.7
    5.6
        Aspartate Aminotransferase (U/L): ≥3xULN(n=75,0)
    2.7
    999
        Cholesterol (mmol/L): >7.72 mmol/L(n=75,72)
    1.3
    1.4
        Gamma Glutamyl Transferase (U/L): ≥3xULN(n=75,72)
    2.7
    6.9
        Glucose (mmol/L): <2.8 mmol/L(n=75,73)
    13.3
    20.5
        Glucose (mmol/L): >19.4 mmol/L(n=75,73)
    10.7
    13.7
        Potassium (mmol/L): <3.0 mmol/L(n=0,72)
    999
    1.4
        Phosphate (mmol/L): >2.00 mmol/L(n=0,72)
    999
    1.4
        Sodium (mmol/L): <130 mmol/L(n=75,0)
    1.3
    999
        Triglycerides (mmol/L): >2.5xULN(n=75,72)
    6.7
    1.4
        Hematocrit (%): >1.2 x ULN(n=74,72)
    9.5
    8.3
        Hemoglobin (g/L): < 0.8 x LLN(n=0,72)
    999
    1.4
        Hemoglobin (g/L): >1.2 x ULN(n=74,72)
    4.1
    2.8
        Erythrocyte MCV (fL): <70 fL(n=74,72)
    2.7
    2.8
        Erythrocyte MCV(fL): >100 fL(n=0,72)
    999
    2.8
        Erythrocytes (10^12/L): >1.2 x ULN(n=74,72)
    1.4
    1.4
        Leukocytes (10^9/L): >1.5 x ULN(n=74,72)
    2.7
    2.8
    No statistical analyses for this end point

    Secondary: Change from Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52

    		Close Top of page
    End point title
    		 Change from Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52
    End point description
    Biomarkers of bone turnover are bone-specific alkaline phosphatase to assess changes in bone formation and C-terminal telopeptide (CTX) to assess changes in bone resorption.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26 and 52
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    67
    68
    Units: units per liter (U/L)
    arithmetic mean (standard deviation)
        Baseline(n=76,75)
    62.09 ± 37.084
    62.62 ± 43.180
        Change From Baseline at Week 26(n=60,59)
    -6.20 ± 18.021
    -7.47 ± 20.139
        Change From Baseline at Week 52(n=49,44)
    -14.36 ± 18.000
    -15.43 ± 22.497
    No statistical analyses for this end point

    Secondary: Change from Baseline in CD26 (CD4+T cells) Surface Antigen Levels at Weeks 26 and 52

    		 Close Top of page
    End point title
    		 Change from Baseline in CD26 (CD4+T cells) Surface Antigen Levels at Weeks 26 and 52
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26 and 52
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    57
    58
    Units: percentage of CD4+ T cells
    arithmetic mean (standard deviation)
        Baseline(n=57,58)
    78.2 ± 8.60
    77.7 ± 7.23
        Change From Baseline at Week 26(n=45,42)
    1.2 ± 6.00
    1.6 ± 7.20
        Change From Baseline at Week 52(n=35,32)
    1.0 ± 5.39
    0.8 ± 4.89
    No statistical analyses for this end point

    Secondary: Change From Baseline in CD26 (CD8+T cells) Surface Antigen Levels at Weeks 26 and 52

    		 Close Top of page
    End point title
    		 Change From Baseline in CD26 (CD8+T cells) Surface Antigen Levels at Weeks 26 and 52
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26 and 52
    End point values
    		 Placebo Alogliptin 25 mg
    Number of subjects analysed
    58
    58
    Units: percentage of CD8+ T cells
    arithmetic mean (standard deviation)
        Baseline
    59.7 ± 13.51
    59.6 ± 15.30
        Change From Baseline at Week 26(n=46,41)
    -0.2 ± 9.15
    1.7 ± 8.76
        Change From Baseline at Week 52(n=37,32)
    1.0 ± 7.63
    -0.3 ± 10.51
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the study start up to end of the study (up to 54 weeks)
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who took at least 1 dose of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Alogliptin matching-placebo tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.

    Reporting group title
    Alogliptin 25 mg
    Reporting group description
    		 Alogliptin 25 mg tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period.

    Serious adverse events
    		 Placebo Alogliptin 25 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 76 (3.95%)
    2 / 75 (2.67%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Forearm fracture
         subjects affected / exposed
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip injury
         subjects affected / exposed
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive urgency
         subjects affected / exposed
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Knee deformity
         subjects affected / exposed
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Alogliptin 25 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    39 / 76 (51.32%)
    31 / 75 (41.33%)
    Investigations
    Glycosylated haemoglobin increased
         subjects affected / exposed
    4 / 76 (5.26%)
    0 / 75 (0.00%)
         occurrences all number
    5
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    8 / 76 (10.53%)
    14 / 75 (18.67%)
         occurrences all number
    10
    19
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    7 / 76 (9.21%)
    7 / 75 (9.33%)
         occurrences all number
    11
    8
    Nausea
         subjects affected / exposed
    5 / 76 (6.58%)
    0 / 75 (0.00%)
         occurrences all number
    6
    0
    Vomiting
         subjects affected / exposed
    6 / 76 (7.89%)
    4 / 75 (5.33%)
         occurrences all number
    9
    5
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 76 (0.00%)
    5 / 75 (6.67%)
         occurrences all number
    0
    9
    Infections and infestations
    Influenza
         subjects affected / exposed
    0 / 76 (0.00%)
    7 / 75 (9.33%)
         occurrences all number
    0
    10
    Sinusitis
         subjects affected / exposed
    4 / 76 (5.26%)
    0 / 75 (0.00%)
         occurrences all number
    4
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 76 (0.00%)
    4 / 75 (5.33%)
         occurrences all number
    0
    5
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    9 / 76 (11.84%)
    9 / 75 (12.00%)
         occurrences all number
    10
    12
    Hypertriglyceridaemia
         subjects affected / exposed
    5 / 76 (6.58%)
    0 / 75 (0.00%)
         occurrences all number
    5
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    5 / 76 (6.58%)
    0 / 75 (0.00%)
         occurrences all number
    5
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Apr 2016
    -Study entry criteria were modified, including broadening HbA1c criteria and hepatic enzyme criteria, in order to better reflect the study population and allow participants with non-alcoholic fatty liver disease (NAFLD) into the study. -The number of schedules was reduced in order to simplify the study design. -A Pre-Randomization Stabilization Period was added for those participants who were not yet stabilized on their current antidiabetic therapy or who have not yet met certain entry criteria. -The guidance for hepatic safety monitoring and withdrawal criteria was revised to reflect the potential inclusion of participants with NAFLD. -The assessment of retinopathy by fundus photography was removed as this microvascular complication is very unlikely to have manifested at this early stage in the natural history of T2DM in this population to warrant evaluation. -Home glucose management and hyperglycemic rescue language were clarified to allow investigators to individualize glucose management based on the needs of the participants and according to local guidance. -The schedule of assessments was adjusted to decrease the number of clinic visits, allow for telephone visits, and minimize fasting requirements in order to reduce the burden on participants.
    08 Nov 2016
    -Added respiratory tract infections and hypersensitivity reactions to the “incidence of infections” in the safety endpoints. -Removed dual-energy x-ray absorptiometry scans. -Added changes from Baseline in microalbuminuria, insulin like growth factor (IGF)-1, and IGF-BP3 as exploratory endpoints. -Modified the length of time for the maintenance of stable anti-hyperglycemic therapy from 1 month to 2 months. -Added recommendations regarding managing insulin therapy. -Clarified that inclusion criteria regarding C-peptide, autoantibodies, age, and BMI apply at randomization and C-peptide, autoantibodies, and BMI criteria apply to participants who have had the diagnosis of T2DM for <1 year and/or who were taking insulin. -Changed eGFR calculations to be based on the Schwartz formula rather than Cockcroft-Gault. -Modified wording of exclusion criteria regarding sexual activity. -Added a randomization criterion for participants on insulin to require and HbA1c level of ≥7.0%. -Updated laboratory testing terminology from islet cell antigen (ICA) 512 antibody to Islet Antigen (IA)-2 antibody. -Added clarification regarding the use of oral or parenteral steroids, wording of the renal safety withdrawal criteria, details regarding assessment of pubertal development, clarification regarding BMI measurements and recommendation for annual ophthalmologic examinations. -Adjusted the volume of blood collected for clinical laboratory samples. -Removed insulin and proinsulin measurements and clarified that C-peptide will only be measured once prior to randomization. -Clarified that glutamic acid decarboxylase (GAD) and IA-2 antibody testing may be performed by the central laboratory. -Added clarification regarding postprandial glucose testing, hematology and serum chemistry testing at the Week -1 Visit. -Clarified that fasting plasma glucose (FPG) testing can be done at the Screening and Week -1 Visits. -Added eGFR measurements at Baseline and at Weeks 26 and 52.
    11 Aug 2020
    -Reduced the sample size from 100 participants per arm to 75 participants per arm. -Removed the specific dropout/hyperglycemic rescue rate of 30%. -Updated text to reflect availability of liraglutide for children and adolescents aged 10 to 17 years. -Added instructions for managing study procedures, data collection, and investigational product during unavoidable circumstances (eg, a widespread disease outbreak such as the COVID-19 pandemic or natural disaster). -Discontinued collection of pharmacogenomic sample. -Added sensitivity analysis for the primary endpoint only that excludes participants affected by COVID-19.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 07 16:19:12 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA