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Efficacy and Safety of TAK-875 Compared to Glimepiride When Used With Metformin in Participants With Type 2 Diabetes

This study has been terminated.
(Due to potential concerns about liver safety (See Detailed Description))
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01481116
First received: November 25, 2011
Last updated: April 24, 2016
Last verified: April 2016
Results First Received: July 24, 2015  
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: TAK-875
Drug: Glimepiride

  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 at 291 sites in Argentina, Australia, Bulgaria, Canada, Colombia, Czech Republic, Estonia, Hong Kong, Israel, Latvia, Lithuania, Malaysia, Mexico, New Zealand, Philippines, Poland, Romania, the Russian Federation, South Africa, Taiwan, Ukraine, the United Kingdom and the United States from 06 November 2011 to 24 April 2014.

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 inadequately controlled while receiving metformin alone were enrolled in 1 of 3 treatment groups as follows: glimepiride; TAK-875 25 milligram (mg); TAK-875 50 mg.

Reporting Groups
  Description
Glimepiride TAK-875 placebo-matching tablets, orally, once daily and glimepiride 1 mg, over-encapsulated capsules, orally, once daily for 1 week followed by up-titration in 2 mg increments up to 6 mg, orally, once daily along with metformin greater than or equal to (>=)1500 mg per day or maximum tolerated dose, tablets, orally for up to 104 weeks. Glimepiride dose could be down-titrated from 6 mg in case of recurrent or severe hypoglycemia.
TAK-875 25 mg TAK-875 25 mg, tablets, orally, once daily and glimepiride placebo-matching capsules, orally, once daily along with metformin >=1500 mg per day or maximum tolerated dose, tablets, orally for up to 104 weeks.
TAK-875 50 mg TAK-875 50 mg, tablets, orally, once daily and glimepiride placebo-matching capsules, orally, once daily along with metformin >=1500 mg per day or maximum tolerated dose, tablets, orally for up to 104 weeks.

Participant Flow:   Overall Study
    Glimepiride     TAK-875 25 mg     TAK-875 50 mg  
STARTED     824     817     813  
Treated     822     816     813  
COMPLETED     0     0     0  
NOT COMPLETED     824     817     813  
Adverse Event                 26                 26                 42  
Major Protocol Deviation                 3                 7                 1  
Lost to Follow-up                 8                 12                 11  
Withdrawal by Subject                 37                 33                 37  
Study Termination                 730                 729                 713  
Pregnancy                 0                 0                 1  
Lack of Efficacy                 3                 3                 1  
Contraindications                 1                 1                 0  
Unspecified                 1                 1                 0  
Participant Started Taking Glipizide                 1                 0                 0  
Participant Moved Out of Area                 2                 0                 1  
Participant Moved Out of Country                 1                 0                 1  
Investigator Decision                 3                 2                 1  
Sponsor Decision                 0                 1                 3  
Non-Compliant With Study Drug                 0                 1                 1  
Investigator's Discretion                 2                 0                 0  
Death                 2                 1                 0  
Hypoglycemic Event                 4                 0                 0  



  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.
The randomized set included all participants who were randomized.

Reporting Groups
  Description
Glimepiride TAK-875 placebo-matching tablets, orally, once daily and glimepiride 1 mg, over-encapsulated capsules, orally, once daily for 1 week followed by up-titration in 2 mg increments up to 6 mg, orally, once daily along with metformin greater than or equal to (>=)1500 mg per day or maximum tolerated dose, tablets, orally for up to 104 weeks. Glimepiride dose could be down-titrated from 6 mg in case of recurrent or severe hypoglycemia.
TAK-875 25 mg TAK-875 25 mg, tablets, orally, once daily and glimepiride placebo-matching capsules, orally, once daily along with metformin >=1500 mg per day or maximum tolerated dose, tablets, orally for up to 104 weeks.
TAK-875 50 mg TAK-875 50 mg, tablets, orally, once daily and glimepiride placebo-matching capsules, orally, once daily along with metformin >=1500 mg per day or maximum tolerated dose, tablets, orally for up to 104 weeks.
Total Total of all reporting groups

Baseline Measures
    Glimepiride     TAK-875 25 mg     TAK-875 50 mg     Total  
Number of Participants  
[units: participants]
  824     817     813     2454  
Age  
[units: years]
Mean (Standard Deviation)
  57.3  (9.56)     56.8  (9.34)     56.6  (9.81)     56.9  (9.57)  
Age, Customized  
[units: participants]
       
Less than (<) 65 years     637     646     648     1931  
>=65 years     187     171     165     523  
Gender  
[units: participants]
       
Female     428     422     362     1212  
Male     396     395     451     1242  
Race/Ethnicity, Customized  
[units: participants]
       
Hispanic or Latino     68     66     70     204  
Non-Hispanic or Latino     105     110     106     321  
Not Available     651     641     637     1929  
Race/Ethnicity, Customized  
[units: participants]
       
American Indian or Alaska Native     8     20     12     40  
Asian     101     99     93     293  
Black or African American     62     70     77     209  
Native Hawaiian or Other Pacific Islander     3     4     7     14  
White     617     598     601     1816  
Multiracial     33     26     23     82  
Region of Enrollment  
[units: participants]
       
Argentina     37     39     37     113  
Australia     4     2     3     9  
Bulgaria     17     18     16     51  
Canada     42     40     39     121  
Colombia     2     0     1     3  
Czech Republic     31     31     31     93  
Estonia     12     12     12     36  
Hong Kong     9     10     10     29  
Israel     50     50     50     150  
Latvia     15     14     14     43  
Lithuania     21     23     22     66  
Malaysia     17     16     17     50  
Mexico     14     14     15     43  
New Zealand     15     14     15     44  
Philippines     39     38     37     114  
Poland     64     66     63     193  
Romania     52     52     51     155  
Russian Federation     26     26     26     78  
South Africa     83     81     83     247  
Taiwan, Province Of China     11     11     12     34  
Ukraine     80     80     79     239  
United Kingdom     18     16     17     51  
United States     165     164     163     492  
Height [1]
[units: centimeter (cm)]
Mean (Standard Deviation)
  166.2  (10.66)     166.2  (10.23)     167.3  (10.19)     166.6  (10.37)  
Weight [2]
[units: kilogram (kg)]
Mean (Standard Deviation)
  86.95  (18.415)     87.35  (18.283)     88.37  (18.796)     87.55  (18.501)  
Body Mass Index (BMI) [3]
[units: kilogram per square meter (kg/m^2)]
Mean (Standard Deviation)
  31.34  (5.334)     31.50  (5.253)     31.43  (5.403)     31.42  (5.329)  
Smoking Classification  
[units: participants]
       
Never smoked     552     533     502     1587  
Current smoker     114     143     126     383  
Ex-smoker     158     141     185     484  
Baseline Glycosylated Hemoglobin (HbA1c) Category  
[units: participants]
       
< 8.5 percent (%)     584     584     592     1760  
>=8.5%     238     232     221     691  
Not Available     2     1     0     3  
Duration of Diabetes [4]
[units: years]
Mean (Standard Deviation)
  6.372  (5.293)     6.566  (5.132)     5.995  (4.711)     6.312  (5.056)  
[1] For this outcome measure, number of participants evaluable were 823, 817 and 813 for each arm, respectively.
[2] For this outcome measure, number of participants evaluable were 822, 816 and 813 for each arm, respectively.
[3] For this outcome measure, number of participants evaluable were 821, 816 and 813 for each arm, respectively.
[4] For this outcome measure, number of participants evaluable were 823, 817 and 812 for each arm, respectively.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in HbA1c at Weeks 78 and 104   [ Time Frame: Baseline and Weeks 78 and 104 ]

2.  Secondary:   Percentage of Participants With Hypoglycemia   [ Time Frame: Day 1 up to Weeks 78 and 104 ]

3.  Secondary:   Change From Baseline in Body Weight at Weeks 78 and 104   [ Time Frame: Baseline and Weeks 78 and 104 ]

4.  Secondary:   Change From Baseline in HbA1c at Weeks 26 and 52   [ Time Frame: Baseline and Weeks 26 and 52 ]

5.  Secondary:   Percentage of Participants With HbA1c <7%   [ Time Frame: Weeks 26, 52, 78 and 104 ]

6.  Secondary:   Percentage of Participants With HbA1c <7% for Participants Who Did Not Report Hypoglycemia   [ Time Frame: Weeks 26, 52, 78 and 104 ]

7.  Secondary:   Change From Baseline in Fasting Plasma Glucose at Weeks 26, 52, 78 and 104   [ Time Frame: Baseline and Weeks 26, 52, 78 and 104 ]


  Serious Adverse Events


  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: Medical Director
Organization: Takeda
phone: +1-877-825-3327
e-mail: clinicaltrialregistry@tpna.com



Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01481116     History of Changes
Other Study ID Numbers: TAK-875_304
2011-001731-24 ( EudraCT Number )
U1111-1124-2296 ( Registry Identifier: WHO )
TAK-875_304CTIL ( Other Identifier: Israel MOH )
DOH-27-0512-3913 ( Registry Identifier: SANCTR )
11-057 ( Registry Identifier: ROCTR )
NMRR-11-882-10318 ( Registry Identifier: NMRR )
HKCTR-1616 ( Registry Identifier: HKUCTR )
262 ( Registry Identifier: RoPCCT )
12/WA/0245 ( Registry Identifier: NRES )
Study First Received: November 25, 2011
Results First Received: July 24, 2015
Last Updated: April 24, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Hong Kong: Department of Health
Taiwan: Department of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: Agência Nacional de Vigilância Sanitária
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech: Statni ustav pro kontrolu leciv
Estonia: The State Agency of Medicine
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Malaysia: National Pharmaceutical Control Bureau
Mexico: Federal Commission for Protection Against Health Risks
New Zealand: Ministry of Health
Philippines: Department of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicine and Medical Devices Agency
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ukraine: The State Expert Center of the Ministry of Ukraine