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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
  Hide Participant Flow

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 
Overall Participants Analyzed 
[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) 
[1] For this outcome measure, number of participants evaluable were 823, 817 and 813 for each arm, respectively.
Weight [1] 
[Units: Kilogram (kg)]
Mean (Standard Deviation)
 86.95  (18.415)   87.35  (18.283)   88.37  (18.796)   87.55  (18.501) 
[1] For this outcome measure, number of participants evaluable were 822, 816 and 813 for each arm, respectively.
Body Mass Index (BMI) [1] 
[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) 
[1] For this outcome measure, number of participants evaluable were 821, 816 and 813 for each arm, respectively.
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 [1] 
[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 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
  Hide Limitations and Caveats

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