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Efficacy and Safety of Alogliptin Compared to Glipizide in Elderly Diabetics

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ClinicalTrials.gov Identifier: NCT00707993
Recruitment Status : Completed
First Posted : July 2, 2008
Results First Posted : May 24, 2013
Last Update Posted : May 24, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus
Interventions Drug: Alogliptin
Drug: Glipizide
Enrollment 441
Recruitment Details Participants enrolled at 110 investigative sites in Hungary, India, Israel, Mexico, Peru, Poland, Romania, Russia, South Africa, the Ukraine and the United States from 25 June 2008 to 30 August 2010.
Pre-assignment Details Participants with a historical diagnosis of type 2 diabetes mellitus were enrolled in one of two, once-daily (QD) treatment groups.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks. Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Period Title: Overall Study
Started 222 219
Completed 133 125
Not Completed 89 94
Reason Not Completed
Adverse Event             16             20
Protocol Violation             4             7
Lost to Follow-up             0             4
Withdrawal by Subject             12             16
Hyperglycemic Rescue             55             47
Other             2             0
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD Total
Hide Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks. Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 222 219 441
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 222 participants 219 participants 441 participants
70.1  (4.42) 69.8  (4.07) 69.9  (4.24)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 222 participants 219 participants 441 participants
<75 years 186 193 379
≥75 years 36 26 62
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 219 participants 441 participants
Female
120
  54.1%
123
  56.2%
243
  55.1%
Male
102
  45.9%
96
  43.8%
198
  44.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 219 participants 441 participants
Hispanic or Latino
79
  35.6%
70
  32.0%
149
  33.8%
Not Hispanic or Latino
143
  64.4%
149
  68.0%
292
  66.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 219 participants 441 participants
American Indian or Alaska Native
12
   5.4%
13
   5.9%
25
   5.7%
Asian
19
   8.6%
26
  11.9%
45
  10.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
16
   7.2%
20
   9.1%
36
   8.2%
White
169
  76.1%
154
  70.3%
323
  73.2%
More than one race
6
   2.7%
6
   2.7%
12
   2.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 222 participants 219 participants 441 participants
78.60  (14.842) 78.81  (15.239) 78.70  (15.024)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 222 participants 219 participants 441 participants
29.58  (4.348) 30.02  (4.459) 29.79  (4.404)
Diabetes duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 222 participants 219 participants 441 participants
6.25  (6.285) 5.94  (6.276) 6.10  (6.275)
Glomerular Filtration Rate (GFR)   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73 m2
Number Analyzed 222 participants 219 participants 441 participants
73.62  (14.762) 72.89  (15.524) 73.26  (15.133)
[1]
Measure Description: Using the Modification of Diet in Renal Disease method.
Smoking history  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 222 participants 219 participants 441 participants
Never smoked 160 168 328
Current smoker 16 11 27
Ex-smoker 46 40 86
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin at Week 52.
Hide Description The change in the percentage of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 or final visit and glycosylated hemoglobin collected at baseline.
Time Frame Baseline and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug, had measurements at Baseline and at the visit, and who met pre-specified criteria (no major protocol violations) for inclusion in the Per Protocol Set. Missing data were imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 180 162
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.14  (0.063) -0.09  (0.067)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alogliptin 25 mg QD, Glipizide 5 mg QD
Comments Primary null hypothesis: the average Week 52 HbA1c change from Baseline for alogliptin is inferior to that for glipizide (1-sided 97.5% CI [alpha=0.025] compared to non-inferiority margin of 0.4%). If the primary null hypothesis was rejected (non-inferiority demonstrated), an additional comparison for statistical superiority of alogliptin was performed. The CI was re-evaluated; statistical superiority declared if the upper limit was < 0%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments Treatment, randomization schedule, and geographic region as class effects; baseline value for the endpoint as a continuous covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.05
Confidence Interval (1-Sided) 97.5%
0.13
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin
Hide Description The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated including final visit relative to baseline.
Time Frame Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34 and Week 42.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug, had measurements at Baseline and at the visit, and who met pre-specified criteria (no major protocol violations) for inclusion in the Per Protocol Set. Missing data were imputed using last observation carried forward (LOCF).
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 180 162
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
Week 4 (n=175; n=148) -0.14  (0.047) -0.11  (0.051)
Week 8 (n=180; n=161) -0.27  (0.051) -0.23  (0.054)
Week 12 (n=180; n=162) -0.34  (0.053) -0.25  (0.055)
Week 16 (n=180; n=162) -0.31  (0.050) -0.32  (0.052)
Week 20 (n=180; n=162) -0.31  (0.051) -0.27  (0.054)
Week 26 (n=180; n=162) -0.28  (0.052) -0.25  (0.055)
Week 34 (n=180; n=162) -0.21  (0.056) -0.21  (0.059)
Week 42 (n=180; n=162) -0.17  (0.062) -0.17  (0.065)
3.Secondary Outcome
Title Incidence of Hypoglycemia
Hide Description Percentage of participants with at least one hypoglycemic episode during 52 week study.
Time Frame On occurrence (up to 52 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
Percentages based on the number of Safety Set participants in each treatment group.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Measure Type: Number
Unit of Measure: percentage of participants
5.4 26.0
4.Secondary Outcome
Title Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL).
Hide Description The number of participants with a fasting plasma glucose value ≥ to 200 mg per dL during the 52 week study.
Time Frame On Occurrence (up to 52 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set).
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Measure Type: Number
Unit of Measure: participants
Baseline to <Week 4 30 17
Week 4 to <Week 8 11 5
Week 8 to <Week 12 12 8
Week 12 to <Week 16 11 8
Week 16 to <Week 20 5 4
Week 20 to <Week 26 2 3
Week 26 to <Week 34 3 8
Week 34 to <Week 42 2 4
Week 42 to Week 52 9 6
Overall 50 37
5.Secondary Outcome
Title Incidence of Hyperglycemic Rescue
Hide Description The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 52 week study.
Time Frame On Occurrence (up to 52 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set). Participants who discontinued prior to Week 2 were excluded from analysis.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Measure Type: Number
Unit of Measure: participants
Week 2 to <Week 4 1 0
Week 4 to <Week 8 2 1
Week 8 to <Week 12 1 0
Week 12 to <Week 16 14 14
Week 16 to <Week 20 6 9
Week 20 to <Week 26 5 8
Week 26 to <Week 34 10 2
Week 34 to <Week 42 6 7
Week 42 to Week 52 10 6
Overall 50 37
6.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose
Hide Description The change in the value of fasting plasma glucose collected at each week indicated including final visit relative to baseline.
Time Frame Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 2 (n=196; n=199) -3.8  (1.93) -5.0  (1.91)
Week 4 (n=217; n=213) -7.7  (1.93) -7.6  (1.95)
Week 8 (n=217; n=214) -8.9  (1.76) -8.7  (1.77)
Week 12 (n=217; n=214) -10.2  (1.84) -9.9  (1.86)
Week 16 (n=217; n=214) -7.9  (1.85) -11.4  (1.86)
Week 20 (n=217; n=214) -9.8  (1.78) -8.7  (1.79)
Week 26 (n=217; n=214) -7.9  (1.97) -6.2  (1.99)
Week 34 (n=217; n=214) -5.4  (1.98) -5.7  (1.99)
Week 42 (n=217; n=214) -3.6  (2.13) -7.4  (2.14)
Week 52 (n=217; n=214) -2.4  (2.24) -4.2  (2.26)
7.Secondary Outcome
Title Change From Baseline in 2-hour Postprandial Glucose
Hide Description The change in postprandial (after eating a meal) glucose levels at week 52 relative to baseline. Standard 2-hour postprandial glucose (PPG) tests performed following an overnight fast and evaluated right before and after a 120-minute (2-hour) timeframe relative to ingestion of a standard oral glucose drink.
Time Frame Baseline and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set).
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 52 PPG level (n=109; n=93) -5.80  (5.530) 6.30  (5.989)
Week 52 PPG excursion (n=109; n=93) 1.82  (4.434) 7.17  (4.804)
8.Secondary Outcome
Title Change From Baseline in Fasting Proinsulin
Hide Description The change between the value of fasting proinsulin collected at each week indicated including final visit relative to baseline.
Time Frame Baseline, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: pmol/L
Week 12 (n=207; n=186) -6.0  (0.99) 1.0  (1.05)
Week 26 (n=211; n=194) -4.6  (1.49) 3.0  (1.56)
Week 42 (n=211; n=194) -4.6  (1.48) 3.1  (1.54)
Week 52 (n=211; n=194) -4.9  (1.42) 3.0  (1.48)
9.Secondary Outcome
Title Change From Baseline in Insulin
Hide Description The change between the value of insulin collected at each week indicated including final visit relative to baseline.
Time Frame Baseline, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mcIU/mL
Week 12 (n=207; n=188) -2.36  (0.673) 0.84  (0.707)
Week 26 (n=210; n=194) -0.41  (1.548) 3.03  (1.611)
Week 42 (n=210; n=194) -0.58  (1.254) 1.53  (1.305)
Week 52 (n=210; n=194) -1.72  (1.731) 3.15  (1.801)
10.Secondary Outcome
Title Change From Baseline in Proinsulin/Insulin Ratio
Hide Description The change between the ratio value of proinsulin and insulin collected at each week indicated including final visit relative to baseline.
Time Frame Baseline, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: ratio
Week 12 (n=206; n=185) -0.288  (0.1035) 0.053  (0.1092)
Week 26 (n=210; n=193) -0.253  (0.4333) 0.562  (0.4520)
Week 42 (n=210; n=193) -0.289  (0.1500) 0.183  (0.1565)
Week 52 (n=210; n=193) -0.155  (0.0899) -0.057  (0.0938)
11.Secondary Outcome
Title Homeostasis Model Assessment of Beta Cell Function
Hide Description The change between homeostasis model assessment of beta cell function collected at each week indicated including final visit relative to baseline. Homeostasis model assessment of beta cell function measures beta cell function, calculated by a constant (20) times insulin, divided by fasting plasma glucose minus a constant (3.5).
Time Frame Baseline, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: percent score of beta cell function
Week 12 (n=203; n=184) -6.104  (8.3062) 30.081  (8.7264)
Week 26 (n=207; n=193) -0.136  (9.7088) 31.669  (10.0562)
Week 42 (n=207; n=193) -5.571  (7.1395) 16.004  (7.3950)
Week 52 (n=207; n=193) -9.755  (13.8868) 35.281  (14.3836)
12.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description The change in body weight measured at each week indicated including final visit from baseline.
Time Frame Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: kg
Week 8 (n=213; n=200) -0.42  (0.118) 0.55  (0.122)
Week 12 (n=215; n=203) -0.52  (0.142) 0.42  (0.146)
Week 26 (n=215; n=204) -0.68  (0.188) 0.66  (0.193)
Week 42 (n=215; n=204) -0.72  (0.211) 0.57  (0.216)
Week 52 (n=215; n=204) -0.62  (0.227) 0.60  (0.233)
13.Secondary Outcome
Title Change From Baseline in Serum Lipids (Total Cholesterol)
Hide Description The change in total cholesterol measured at each week indicated including final visit from baseline.
Time Frame Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 8 (n=208; n=195) -5.6  (2.01) -1.6  (2.08)
Week 12 (n=213; n=201) -4.2  (2.06) -0.7  (2.12)
Week 26 (n=213; n=201) 1.6  (2.03) 0.1  (2.09)
Week 42 (n=213; n=201) 0.2  (2.07) 0.1  (2.13)
Week 52 (n=213; n=201) -0.8  (2.28) -0.5  (2.35)
14.Secondary Outcome
Title Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol)
Hide Description The change in high-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.
Time Frame Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 8 (n=206; n=193) -0.1  (0.59) 1.2  (0.61)
Week 12 (n=212; n=201) 0.4  (0.47) 0.5  (0.48)
Week 26 (n=212; n=201) 1.7  (0.50) 0.2  (0.52)
Week 42 (n=212; n=201) 1.4  (0.59) 0.1  (0.61)
Week 52 (n=212; n=201) 0.8  (0.50) 0.3  (0.51)
15.Secondary Outcome
Title Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol)
Hide Description The change in low-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.
Time Frame Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 8 (n=200; n=185) -3.2  (1.70) -2.8  (1.76)
Week 12 (n=208; n=195) -2.0  (1.75) -2.4  (1.81)
Week 26 (n=208; n=196) 3.1  (1.67) -1.1  (1.72)
Week 42 (n=208; n=197) 1.2  (1.79) -0.8  (1.84)
Week 52 (n=209; n=197) 0.9  (1.83) -1.4  (1.88)
16.Secondary Outcome
Title Change From Baseline in Serum Lipids (Triglycerides)
Hide Description The change in triglycerides measured at each week indicated including final visit from baseline.
Time Frame Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 8 (n=208; n=195) -12.8  (5.04) 2.7  (5.20)
Week 12 (n=213; n=201) -15.5  (5.72) 7.5  (5.89)
Week 26 (n=213; n=201) -16.3  (4.74) 3.9  (4.88)
Week 42 (n=213; n=201) -12.6  (5.01) 5.5  (5.16)
Week 52 (n=213; n=201) -13.2  (5.27) 1.9  (5.42)
17.Secondary Outcome
Title Change From Baseline in High Sensitivity C-reactive Protein
Hide Description The change between the high sensitivity C-reactive protein value collected at each week indicated including final visit from baseline.
Time Frame Baseline, Week 12, Week 26, Week 42 and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Least Squares Mean (Standard Error)
Unit of Measure: mg/L
Week 12 (n=209; n=192) 0.45  (0.699) 0.10  (0.730)
Week 26 (n=212; n=198) -0.02  (0.682) 0.47  (0.706)
Week 42 (n=212; n=198) 0.33  (0.736) 0.53  (0.762)
Week 52 (n=212; n=198) 0.01  (0.656) 0.21  (0.679)
18.Secondary Outcome
Title Incidence of Subjects Achieving Glycosylated Hemoglobin <=7%
Hide Description The percentage of participants with a value for the percentage of glycosylated hemoglobin (HbA1c; the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5 and 7.0% during the 52 week study.
Time Frame Baseline and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c ≤6.5% 22.3 18.2
HbA1c ≤7.0% 48.8 45.3
19.Secondary Outcome
Title Incidence of Glycosylated Hemoglobin Decrease From Baseline.
Hide Description The percentage of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5, 1.0, 1.5 and 2.0% during the 52 week study.
Time Frame Baseline and Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description:
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Overall Number of Participants Analyzed 222 219
Measure Type: Number
Unit of Measure: percentage of participants
Decrease from Baseline in HbA1c ≥0.5% 32.1 29.0
Decrease from Baseline in HbA1c ≥1.0% 12.6 10.3
Decrease from Baseline in HbA1c ≥1.5% 5.1 2.3
Decrease from Baseline in HbA1c ≥2.0% 2.8 1.4
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days after the last dose of double-blind study drug.
Adverse Event Reporting Description At each visit the investigator was 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.
 
Arm/Group Title Alogliptin 25 mg QD Glipizide 5 mg QD
Hide Arm/Group Description Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks. Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
All-Cause Mortality
Alogliptin 25 mg QD Glipizide 5 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Alogliptin 25 mg QD Glipizide 5 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   16/222 (7.21%)   13/219 (5.94%) 
Cardiac disorders     
Angina pectoris  1  1/222 (0.45%)  0/219 (0.00%) 
Cardiac failure  1  1/222 (0.45%)  0/219 (0.00%) 
Cardiac failure congestive  1  1/222 (0.45%)  1/219 (0.46%) 
Coronary artery disease  1  1/222 (0.45%)  0/219 (0.00%) 
Ischaemic cardiomyopathy  1  0/222 (0.00%)  1/219 (0.46%) 
Left ventricular failure  1  1/222 (0.45%)  0/219 (0.00%) 
Myocardial infarction  1  0/222 (0.00%)  1/219 (0.46%) 
Ear and labyrinth disorders     
Sudden hearing loss  1  1/222 (0.45%)  0/219 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  1/222 (0.45%)  0/219 (0.00%) 
Cholecystitis acute  1  1/222 (0.45%)  1/219 (0.46%) 
Cholelithiasis  1  0/222 (0.00%)  2/219 (0.91%) 
Infections and infestations     
Diverticulitis  1  1/222 (0.45%)  0/219 (0.00%) 
Pyelonephritis acute  1  0/222 (0.00%)  1/219 (0.46%) 
Respiratory tract infection viral  1  0/222 (0.00%)  1/219 (0.46%) 
Urosepsis  1  0/222 (0.00%)  1/219 (0.46%) 
Injury, poisoning and procedural complications     
Fall  1  2/222 (0.90%)  0/219 (0.00%) 
Graft thrombosis  1  0/222 (0.00%)  1/219 (0.46%) 
Multiple fractures  1  1/222 (0.45%)  0/219 (0.00%) 
Postoperative fever  1  1/222 (0.45%)  0/219 (0.00%) 
Seroma  1  1/222 (0.45%)  0/219 (0.00%) 
Stress fracture  1  0/222 (0.00%)  1/219 (0.46%) 
Upper limb fracture  1  1/222 (0.45%)  0/219 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  1/222 (0.45%)  0/219 (0.00%) 
Cervix carcinoma  1  1/222 (0.45%)  0/219 (0.00%) 
Nervous system disorders     
Cerebrovascular accident  1  0/222 (0.00%)  1/219 (0.46%) 
Dizziness  1  0/222 (0.00%)  1/219 (0.46%) 
Transient ischaemic attack  1  1/222 (0.45%)  0/219 (0.00%) 
Renal and urinary disorders     
Calculus ureteric  1  1/222 (0.45%)  0/219 (0.00%) 
Renal failure acute  1  0/222 (0.00%)  1/219 (0.46%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  1/222 (0.45%)  0/219 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary hypertension  1  1/222 (0.45%)  0/219 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Alogliptin 25 mg QD Glipizide 5 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   103/222 (46.40%)   105/219 (47.95%) 
Gastrointestinal disorders     
Diarrhoea  1  9/222 (4.05%)  14/219 (6.39%) 
Dyspepsia  1  7/222 (3.15%)  1/219 (0.46%) 
Nausea  1  7/222 (3.15%)  8/219 (3.65%) 
General disorders     
Pyrexia  1  2/222 (0.90%)  7/219 (3.20%) 
Infections and infestations     
Bronchitis  1  6/222 (2.70%)  9/219 (4.11%) 
Nasopharyngitis  1  13/222 (5.86%)  10/219 (4.57%) 
Pharyngitis  1  5/222 (2.25%)  7/219 (3.20%) 
Upper respiratory tract infection  1  12/222 (5.41%)  5/219 (2.28%) 
Urinary tract infection  1  26/222 (11.71%)  23/219 (10.50%) 
Investigations     
C-reactive protein increased  1  9/222 (4.05%)  3/219 (1.37%) 
Metabolism and nutrition disorders     
Dyslipidaemia  1  5/222 (2.25%)  10/219 (4.57%) 
Hypoglycaemia  1  0/222 (0.00%)  8/219 (3.65%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  10/222 (4.50%)  12/219 (5.48%) 
Back pain  1  9/222 (4.05%)  11/219 (5.02%) 
Osteoarthritis  1  3/222 (1.35%)  8/219 (3.65%) 
Pain in extremity  1  6/222 (2.70%)  7/219 (3.20%) 
Nervous system disorders     
Dizziness  1  13/222 (5.86%)  18/219 (8.22%) 
Headache  1  16/222 (7.21%)  15/219 (6.85%) 
Vascular disorders     
Hypertension  1  12/222 (5.41%)  10/219 (4.57%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
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Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
EMail: clinicaltrialregistry@tpna.com
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00707993     History of Changes
Other Study ID Numbers: SYR-322_303
2008-000959-10 ( Registry Identifier: EudraCT )
U1111-1112-7905 ( Registry Identifier: WHO )
First Submitted: June 27, 2008
First Posted: July 2, 2008
Results First Submitted: February 17, 2013
Results First Posted: May 24, 2013
Last Update Posted: May 24, 2013