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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  
Number of Participants  
[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  
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 [2]
[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)  
Height [3]
[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)  
Body Mass Index (BMI) [4]
[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)  
BMI Category [4]
[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  
Glycosylated Hemoglobin (HbA1c) [5]
[units: percent]
Mean (Standard Deviation)
  8.34  (0.739)     8.35  (0.694)     8.41  (0.712)     8.43  (0.765)     NA [6]
HbA1c Category [7]
[units: participants]
         
< 8.5%     80     156     154     148     538  
≥ 8.5%     52     104     109     112     377  
Data Not Available     0     0     0     1     1  
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 [8]
[units: ng/dL]
Mean (Standard Deviation)
  178.4  (36.94)     175.6  (37.67)     179.0  (33.52)     180.0  (37.98)     NA [9]
[1] Race data is available for 260 participants in the fasiglifam 50 mg treatment arm.
[2] Weight data is available for 260 participants in the fasiglifam 50 mg treatment arm.
[3] Height data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.
[4] BMI data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.
[5] HbA1c data is available for 258 and 260 participants in the sitagliptin 100 mg and fasiglifam 50 mg treatment arms, respectively.
[6] Not determined
[7] HbA1c data is available for 260 participants in the fasiglifam 50 mg treatment arm.
[8] Data is only available for 258 and 259 participants in the sitagliptin 100 mg and fasiglifam 50 mg treatment arms, respectively.
[9] 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
No text entered.


  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