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Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes

This study has been terminated.
(Due to concerns about potential liver safety (See Detailed Description))
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01549964
First received: March 6, 2012
Last updated: April 20, 2016
Last verified: April 2016
Results First Received: March 25, 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: Glycemic Control
Interventions: Drug: Fasiglifam (TAK-875)
Drug: Sitagliptin
Drug: Placebo

  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 168 investigative sites in Australia, Bulgaria, Croatia, Czech Republic, Hungary, Italy, Korea, Republic, Malaysia, Slovakia, Thailand and the United States from 05 April 2012 to 27 March 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of Type 2 Diabetes Mellitus were randomly enrolled in 1 of 4 treatment groups in a 1:2:2:2 ratio, once a day placebo, 100 mg sitagliptin, 25 mg fasiglifam or 50 mg fasiglifam in combination with metformin.

Reporting Groups
  Description
Placebo Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Sitagliptin 100 mg Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Participant Flow for 2 periods

Period 1:   24-Week Treatment Period
    Placebo   Sitagliptin 100 mg   Fasiglifam 25 mg   Fasiglifam 50 mg
STARTED   132   260   263   261 
Safety Analysis Set=Received Treatment   132   260   263   260 
COMPLETED   71   149   147   140 
NOT COMPLETED   61   111   116   121 
Study Terminated by Sponsor                50                104                104                105 
Voluntary Withdrawal                6                3                3                8 
Pretreatment Event/Adverse Event                1                4                4                4 
Lost to Follow-up                1                0                1                2 
Lack of Efficacy                1                0                1                1 
Other                1                0                1                0 
Metformin/Sitagliptin Contraindication                0                0                1                0 
Randomized but Not Treated                0                0                0                1 
Completion Status Unknown                1                0                1                0 

Period 2:   80-Week Extension Period
    Placebo   Sitagliptin 100 mg   Fasiglifam 25 mg   Fasiglifam 50 mg
STARTED   66   138   140   137 
COMPLETED   0   0   0   0 
NOT COMPLETED   66   138   140   137 
Pregnancy                0                0                1                0 
Study Terminated by Sponsor                65                137                132                132 
Voluntary Withdrawal                0                1                4                2 
Lost to Follow-up                1                0                2                1 
Pretreatment Event/Adverse Event                0                0                1                2 



  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 Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Sitagliptin 100 mg Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Total Total of all reporting groups

Baseline Measures
   Placebo   Sitagliptin 100 mg   Fasiglifam 25 mg   Fasiglifam 50 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 132   260   263   261   916 
Age 
[Units: Years]
Mean (Standard Deviation)
 55.6  (9.72)   55.8  (9.84)   56.3  (9.58)   56.0  (9.37)   56.0  (9.60) 
Age, Customized 
[Units: Participants]
         
< 65 years   107   214   216   220   757 
≥ 65 years   25   46   47   41   159 
Gender 
[Units: Participants]
         
Female   66   103   127   126   422 
Male   66   157   136   135   494 
Race/Ethnicity, Customized [1] 
[Units: Participants]
         
American Indian or Alaska Native   0   0   2   3   5 
Asian   12   30   28   26   96 
Black or African American   8   13   19   12   52 
Native Hawaiian or Other Pacific Islander   0   0   0   2   2 
White   112   216   214   217   759 
Multiracial   0   1   0   0   1 
Data Not Available   0   0   0   1   1 
[1] Race data is available for 260 participants in the fasiglifam 50 mg treatment arm.
Race/Ethnicity, Customized 
[Units: Participants]
         
Hispanic or Latino   13   29   28   28   98 
Non-Hispanic or Latino   28   59   53   55   195 
Not Collected   91   172   182   178   623 
Region of Enrollment 
[Units: Participants]
         
Australia   3   5   5   5   18 
Bulgaria   3   7   7   7   24 
Croatia   4   6   8   6   24 
Czech Republic   8   15   14   14   51 
Hungary   29   56   61   60   206 
Italy   1   3   3   2   9 
Korea, Republic Of   2   4   4   2   12 
Malaysia   2   8   7   8   25 
Slovakia   34   66   65   66   231 
Thailand   7   14   13   14   48 
United States   39   76   76   77   268 
Weight [1] 
[Units: Kg]
Mean (Standard Deviation)
 91.15  (18.988)   91.41  (19.664)   91.44  (17.859)   91.53  (18.772)   91.42  (18.776) 
[1] Weight data is available for 260 participants in the fasiglifam 50 mg treatment arm.
Height [1] 
[Units: Cm]
Mean (Standard Deviation)
 168.2  (10.08)   169.4  (10.74)   168.5  (10.53)   168.4  (9.85)   168.7  (10.34) 
[1] Height data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.
Body Mass Index (BMI) [1] 
[Units: Kg/m^2]
Mean (Standard Deviation)
 32.06  (5.070)   31.68  (5.282)   32.11  (5.126)   32.16  (5.651)   32.00  (5.312) 
[1] BMI data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.
BMI Category [1] 
[Units: Participants]
         
< 30 kg/m^2   53   106   92   101   352 
≥ 30 kg/m^2   79   154   170   159   562 
Data Not Available   0   0   1   1   2 
[1] BMI data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.
Glycosylated Hemoglobin (HbA1c) [1] [2] 
[Units: Percent]
Mean (Standard Deviation)
 8.34  (0.739)   8.35  (0.694)   8.41  (0.712)   8.43  (0.765)   NA [2] 
[1] HbA1c data is available for 258 and 260 participants in the sitagliptin 100 mg and fasiglifam 50 mg treatment arms, respectively.
[2] Not determined
HbA1c Category [1] 
[Units: Participants]
         
< 8.5%   80   156   154   148   538 
≥ 8.5%   52   104   109   112   377 
Data Not Available   0   0   0   1   1 
[1] HbA1c data is available for 260 participants in the fasiglifam 50 mg treatment arm.
Duration of Diabetes 
[Units: Years]
Mean (Standard Deviation)
 6.655  (6.262)   5.940  (4.942)   6.726  (4.615)   6.375  (5.214)   6.393  (5.143) 
Fasting Plasma Glucose [1] [2] 
[Units: ng/dL]
Mean (Standard Deviation)
 178.4  (36.94)   175.6  (37.67)   179.0  (33.52)   180.0  (37.98)   NA [2] 
[1] Data is only available for 258 and 259 participants in the sitagliptin 100 mg and fasiglifam 50 mg treatment arms, respectively.
[2] Not determined.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c)   [ Time Frame: Baseline and Week 24 ]

2.  Secondary:   Incidence of HbA1c <7%   [ Time Frame: 24 Weeks ]

3.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG)   [ Time Frame: Baseline and Week 24 ]


  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, Clinical Science
Organization: Takeda
phone: +1-877-825-3327
e-mail: clinicaltrialregistry@tpna.com



Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01549964     History of Changes
Other Study ID Numbers: TAK-875_302
2011-001752-10 ( EudraCT Number )
U1111-1124-2225 ( Registry Identifier: WHO )
NMRR-12-446-11314 ( Registry Identifier: NMRR (Malaysia) )
Study First Received: March 6, 2012
Results First Received: March 25, 2015
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
Croatia: Ministry of Health and Social Care
Hungary: National Institute of Pharmacy
Slovakia: State Institute for Drug Control
Australia: Department of Health and Ageing Therapeutic Goods Administration
Thailand: Food and Drug Administration