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Efficacy and Safety of Alogliptin in Participants With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01289119
First received: February 1, 2011
Last updated: February 17, 2013
Last verified: February 2013
Results First Received: February 17, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Alogliptin
Drug: Placebo to alogliptin
Drug: Metformin
Drug: Pioglitazone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 30 investigative sites in China, Taiwan province and Hong Kong from 23 December 2010 to 19 December 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a historical diagnosis of Type 2 diabetes mellitus who were experiencing inadequate glycemic control were stratified into 1 of the 3 therapy groups based upon their background antidiabetic therapy before being randomized 1:1 to receive either alogliptin 25 mg once daily or matching placebo once daily.

Reporting Groups
  Description
Placebo Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Alogliptin Monotherapy Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Metformin Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Metformin + Alogliptin Add-on Therapy Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Pioglitazone Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Pioglitazone + Alogliptin Add-on Therapy Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.

Participant Flow:   Overall Study
    Placebo   Alogliptin Monotherapy   Metformin   Metformin + Alogliptin Add-on Therapy   Pioglitazone   Pioglitazone + Alogliptin Add-on Therapy
STARTED   93   92   98   99   63   61 
Treated   92 [1]   92   98   99   63   61 
COMPLETED   84   83   89   93   58   57 
NOT COMPLETED   9   9   9   6   5   4 
Adverse Event                2                1                0                2                1                0 
Major Protocol Deviation                2                1                3                0                2                1 
Lost to Follow-up                0                3                0                0                0                1 
Withdrawal by Subject                4                2                4                3                1                1 
Pregnancy                0                1                0                0                0                0 
Lack of Efficacy                0                1                1                1                1                1 
Other                1                0                1                0                0                0 
[1] Patients who took at least one dose of double-blind study drug.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Alogliptin Monotherapy Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Metformin Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Metformin + Alogliptin Add-on Therapy Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Pioglitazone Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Pioglitazone + Alogliptin Add-on Therapy Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Total Total of all reporting groups

Baseline Measures
   Placebo   Alogliptin Monotherapy   Metformin   Metformin + Alogliptin Add-on Therapy   Pioglitazone   Pioglitazone + Alogliptin Add-on Therapy   Total 
Overall Participants Analyzed 
[Units: Participants]
 93   92   98   99   63   61   506 
Age 
[Units: Years]
Mean (Standard Deviation)
 53.1  (8.88)   51.6  (10.41)   53.2  (9.46)   53.0  (9.88)   51.8  (10.37)   52.6  (9.44)   52.6  (9.71) 
Age, Customized 
[Units: Participants]
             
<65 Years   81   80   86   85   56   52   440 
≥65 years   12   12   12   14   7   9   66 
Gender 
[Units: Participants]
             
Female   39   37   50   48   24   33   231 
Male   54   55   48   51   39   28   275 
Race/Ethnicity, Customized 
[Units: Participants]
 93   92   98   99   63   61   506 
Region of Enrollment 
[Units: Participants]
             
Taiwan   1   0   2   3   0   0   6 
Hong Kong   1   2   2   4   0   0   9 
China   91   90   94   92   63   61   491 
Height 
[Units: Cm]
Mean (Standard Deviation)
 165.4  (7.19)   165.9  (8.61)   164.8  (8.47)   165.7  (9.06)   166.2  (8.87)   163.0  (7.06)   165.2  (8.31) 
Weight 
[Units: Kg]
Mean (Standard Deviation)
 70.86  (10.464)   71.16  (11.065)   69.67  (11.792)   71.20  (13.473)   72.44  (11.989)   67.59  (11.989)   70.55  (11.856) 
Body Mass Index (BMI) 
[Units: Kg/m^2]
Mean (Standard Deviation)
 25.86  (3.002)   25.79  (3.086)   25.54  (2.876)   25.75  (3.122)   26.13  (3.031)   25.32  (3.223)   25.73  (3.042) 
Diabetes duration 
[Units: Years]
Mean (Standard Deviation)
 2.12  (2.845)   1.86  (2.369)   5.33  (3.873)   5.38  (4.335)   4.85  (4.724)   5.80  (5.300)   4.11  (4.215) 
HbA1c 
[Units: Participants]
             
<8.0%   47   48   54   55   34   32   270 
≥8.0%   46   44   44   44   29   29   236 
Stable Daily Dose of Metformin [1] [2] 
[Units: Mg]
Mean (Standard Deviation)
 NA [2]   NA [2]   1484.2  (451.09)   1472.2  (417.31)   1355.0  (431.80)   1295.0  (506.82)   1426.6  (450.90) 
[1] Participant population for this measure for each treatment arm: 0, 0, 98, 99, 50, 50; Total population: 297
[2] Participants in this arm were not taking Metformin
Stable Daily Dose of Pioglitazone [1] [2] 
[Units: Mg]
Mean (Standard Deviation)
 NA [2]   NA [2]   NA [2]   NA [2]   21.9  (11.37)   20.2  (7.19)   21.0  (9.55) 
[1] Participant population for this measure for each treatment arm: 0, 0, 0, 0, 63, 61; Total population: 124
[2] Participants in this arm were not taking Pioglitazone


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c)   [ Time Frame: Baseline and Week 16. ]

2.  Secondary:   Change From Baseline in HbA1c Over Time   [ Time Frame: Baseline and Weeks 4, 8 and 12. ]

3.  Secondary:   Change From Baseline in Fasting Plasma Glucose Over Time   [ Time Frame: Baseline and Weeks 4, 8, 12 and 16. ]

4.  Secondary:   Percentage of Participants With Marked Hyperglycemia   [ Time Frame: Randomization to Week 16. ]

5.  Secondary:   Change From Baseline in Body Weight   [ Time Frame: Baseline and Weeks 8 and 16. ]

6.  Secondary:   Percentage of Participants With HbA1c ≤6.5% at Week 16   [ Time Frame: Week 16 ]

7.  Secondary:   Percentage of Participants With HbA1c ≤7.0% at Week 16   [ Time Frame: Week 16 ]

8.  Secondary:   Percentage of Participants With HbA1c ≤7.5% at Week 16   [ Time Frame: Week 16 ]

9.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥ 0.5%   [ Time Frame: Baseline and Week 16 ]

10.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥1.0%   [ Time Frame: Baseline and Week 16 ]

11.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥1.5%   [ Time Frame: Baseline and Week 16. ]

12.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥2.0%   [ Time Frame: Baseline and Week 16. ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame Treatment-emergent adverse events (TEAE) were defined as any adverse events that started on or after the date of the first dose of double-blind study drug and within 14 days after the date of the last dose of double-blind study drug.
Additional Description The investigator had to document any occurrence of adverse events at each visit, and the occurrence of abnormal laboratory findings at applicable visits. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Reporting Groups
  Description
Placebo Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Alogliptin Monotherapy Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Metformin Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Metformin + Alogliptin Add-on Therapy Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Pioglitazone Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Pioglitazone + Alogliptin Add-on Therapy Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.

Serious Adverse Events
    Placebo   Alogliptin Monotherapy   Metformin   Metformin + Alogliptin Add-on Therapy   Pioglitazone   Pioglitazone + Alogliptin Add-on Therapy
Total, serious adverse events             
# participants affected / at risk   2/92 (2.17%)   2/92 (2.17%)   3/98 (3.06%)   0/99 (0.00%)   0/63 (0.00%)   1/61 (1.64%) 
Cardiac disorders             
Atrial fibrillation † 1             
# participants affected / at risk   0/92 (0.00%)   0/92 (0.00%)   1/98 (1.02%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Coronary artery disease † 1             
# participants affected / at risk   0/92 (0.00%)   0/92 (0.00%)   1/98 (1.02%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Gastrointestinal disorders             
Pancreatitis acute † 1             
# participants affected / at risk   1/92 (1.09%)   0/92 (0.00%)   0/98 (0.00%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Hepatobiliary disorders             
Cholangitis acute † 1             
# participants affected / at risk   0/92 (0.00%)   1/92 (1.09%)   0/98 (0.00%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Infections and infestations             
Cellulitis † 1             
# participants affected / at risk   1/92 (1.09%)   0/92 (0.00%)   0/98 (0.00%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Musculoskeletal and connective tissue disorders             
Intervertebral disc protrusion † 1             
# participants affected / at risk   0/92 (0.00%)   0/92 (0.00%)   1/98 (1.02%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Intraductal papilloma of breast † 1             
# participants affected / at risk   0/92 (0.00%)   1/92 (1.09%)   0/98 (0.00%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Nervous system disorders             
Lacunar infarction † 1             
# participants affected / at risk   0/92 (0.00%)   0/92 (0.00%)   0/98 (0.00%)   0/99 (0.00%)   0/63 (0.00%)   1/61 (1.64%) 
Vascular disorders             
Hypertension † 1             
# participants affected / at risk   0/92 (0.00%)   0/92 (0.00%)   1/98 (1.02%)   0/99 (0.00%)   0/63 (0.00%)   0/61 (0.00%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA version 14.1




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com



Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01289119     History of Changes
Other Study ID Numbers: SYR-322_02
U1111-1118-3681 ( Registry Identifier: WHO )
SYR-322_308 ( Other Identifier: Takeda ID )
Study First Received: February 1, 2011
Results First Received: February 17, 2013
Last Updated: February 17, 2013
Health Authority: China: Ministry of Health
Hong Kong: Department of Health
Taiwan : Food and Drug Administration