ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01549964
Recruitment Status : Terminated (Due to concerns about potential liver safety (See Detailed Description))
First Posted : March 9, 2012
Results First Posted : June 2, 2016
Last Update Posted : June 2, 2016
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Glycemic Control
Interventions Drug: Fasiglifam (TAK-875)
Drug: Sitagliptin
Drug: Placebo
Enrollment 916
Recruitment Details 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 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.
Arm/Group Title Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Hide Arm/Group Description 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, 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, 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, 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.
Period Title: 24-Week Treatment Period
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
Reason Not Completed
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 Title: 80-Week Extension Period
Started 66 138 140 137
Completed 0 0 0 0
Not Completed 66 138 140 137
Reason Not Completed
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
Arm/Group Title Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg Total
Hide Arm/Group Description 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, 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, 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, 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 of all reporting groups
Overall Number of Baseline Participants 132 260 263 261 916
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
55.6  (9.72) 55.8  (9.84) 56.3  (9.58) 56.0  (9.37) 56.0  (9.60)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
< 65 years 107 214 216 220 757
≥ 65 years 25 46 47 41 159
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
Female
66
  50.0%
103
  39.6%
127
  48.3%
126
  48.3%
422
  46.1%
Male
66
  50.0%
157
  60.4%
136
  51.7%
135
  51.7%
494
  53.9%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 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]
Measure Description: Race data is available for 260 participants in the fasiglifam 50 mg treatment arm.
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 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] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
91.15  (18.988) 91.41  (19.664) 91.44  (17.859) 91.53  (18.772) 91.42  (18.776)
[1]
Measure Description: Weight data is available for 260 participants in the fasiglifam 50 mg treatment arm.
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
168.2  (10.08) 169.4  (10.74) 168.5  (10.53) 168.4  (9.85) 168.7  (10.34)
[1]
Measure Description: 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] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
32.06  (5.070) 31.68  (5.282) 32.11  (5.126) 32.16  (5.651) 32.00  (5.312)
[1]
Measure Description: BMI data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.
BMI Category   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 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]
Measure Description: 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] 
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
8.34  (0.739) 8.35  (0.694) 8.41  (0.712) 8.43  (0.765) NA [2]   (NA)
[1]
Measure Description: 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
< 8.5% 80 156 154 148 538
≥ 8.5% 52 104 109 112 377
Data Not Available 0 0 0 1 1
[1]
Measure Description: HbA1c data is available for 260 participants in the fasiglifam 50 mg treatment arm.
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
6.655  (6.262) 5.940  (4.942) 6.726  (4.615) 6.375  (5.214) 6.393  (5.143)
Fasting Plasma Glucose   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/dL
Number Analyzed 132 participants 260 participants 263 participants 261 participants 916 participants
178.4  (36.94) 175.6  (37.67) 179.0  (33.52) 180.0  (37.98) NA [2]   (NA)
[1]
Measure Description: Data is only available for 258 and 259 participants in the sitagliptin 100 mg and fasiglifam 50 mg treatment arms, respectively.
[2]
Not determined.
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Hide Description The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to Baseline. A Mixed Model Repeated Measures (MMRM) model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all randomized participants who received at least 1 dose of study drug analyzed according to the treatment group to which they were randomized. A participant was included in the analyses when there was both a Baseline and at least 1 Post-baseline value at Week 24.
Arm/Group Title Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Hide Arm/Group Description:
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, 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, 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, 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.
Overall Number of Participants Analyzed 67 145 144 138
Least Squares Mean (Standard Error)
Unit of Measure: Percent
-0.19  (0.098) -1.07  (0.074) -0.75  (0.073) -1.01  (0.074)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fasiglifam 25 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.55
Confidence Interval (2-Sided) 95%
-0.77 to -0.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.108
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sitagliptin 100 mg, Fasiglifam 25 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.15 to 0.49
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.087
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Fasiglifam 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.82
Confidence Interval (2-Sided) 95%
-1.03 to -0.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.109
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sitagliptin 100 mg, Fasiglifam 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.524
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.12 to 0.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.087
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Incidence of HbA1c <7%
Hide Description Incidence (percentage) of participants with glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than 7% at Week 24.
Time Frame 24 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all randomized participants who received at least 1 dose of study drug analyzed according to the treatment group to which they were randomized
Arm/Group Title Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Hide Arm/Group Description:
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, 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, 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, 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.
Overall Number of Participants Analyzed 67 145 144 138
Measure Type: Number
Unit of Measure: percentage of participants
14.9 42.8 24.3 37.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fasiglifam 25 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments P-Value was obtained from a logistic model with treatment, schedule, baseline HbA1c as explanatory variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
1.00 to 5.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sitagliptin 100 mg, Fasiglifam 25 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-Value was obtained from a logistic model with treatment, schedule, baseline HbA1c as explanatory variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.23 to 0.67
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Fasiglifam 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-Value was obtained from a logistic model with treatment, schedule, baseline HbA1c as explanatory variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.06
Confidence Interval (2-Sided) 95%
2.24 to 11.42
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sitagliptin 100 mg, Fasiglifam 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.493
Comments P-Value was obtained from a logistic model with treatment, schedule, baseline HbA1c as explanatory variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.50 to 1.39
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG)
Hide Description The change between FPG collected at week 24 relative to Baseline. A MMRM model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all randomized participants who received at least 1 dose of study drug analyzed according to the treatment group to which they were randomized. A participant was included in the analyses when there was both a Baseline and at least 1 Post-baseline value at Week 24.
Arm/Group Title Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Hide Arm/Group Description:
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, 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, 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, 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.
Overall Number of Participants Analyzed 67 145 142 135
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-1.6  (4.07) -21.7  (3.13) -26.9  (3.13) -32.9  (3.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fasiglifam 25 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -25.2
Confidence Interval (2-Sided) 95%
-33.8 to -16.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.36
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sitagliptin 100 mg, Fasiglifam 25 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.142
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.1
Confidence Interval (2-Sided) 95%
-12.0 to 1.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.49
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Fasiglifam 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -31.3
Confidence Interval (2-Sided) 95%
-39.9 to -22.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.40
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sitagliptin 100 mg, Fasiglifam 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.
Method Mixed model for repeated measurements
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean difference
Estimated Value -11.2
Confidence Interval (2-Sided) 95%
-18.1 to -4.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.53
Estimation Comments [Not Specified]
Time Frame First dose of study medication to 30 day past last dose of study medication (Up to 637 days)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Hide Arm/Group Description 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, 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, 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, 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.
All-Cause Mortality
Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/132 (1.52%)   10/260 (3.85%)   14/263 (5.32%)   4/260 (1.54%) 
Blood and lymphatic system disorders         
Anaemia  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Cardiac disorders         
Atrioventricular block first degree  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Coronary artery disease  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Cardiac failure  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Angina unstable  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Congenital, familial and genetic disorders         
Phimosis  1  1/132 (0.76%)  0/260 (0.00%)  0/263 (0.00%)  0/260 (0.00%) 
Gastrointestinal disorders         
Pancreatitis  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
General disorders         
Non-cardiac chest pain  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Hepatobiliary disorders         
Cholecystitis  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Cholelithiasis  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Liver disorder  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Bile duct stone  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Infections and infestations         
Gangrene  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Hepatitis B  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Bronchopneumonia  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Pneumonia  1  0/132 (0.00%)  0/260 (0.00%)  0/263 (0.00%)  1/260 (0.38%) 
Sepsis  1 [1]  0/132 (0.00%)  2/260 (0.77%)  0/263 (0.00%)  0/260 (0.00%) 
Erysipelas  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Injury, poisoning and procedural complications         
Radius fracture  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Aspartate aminotransferase increased  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Blood bilirubin increased  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Liver function test abnormal  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Carotid bruit  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Musculoskeletal and connective tissue disorders         
Intervertebral disc disorder  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer female  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Tumour of ampulla of Vater  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Oesophageal carcinoma  1 [2]  1/132 (0.76%)  0/260 (0.00%)  0/263 (0.00%)  0/260 (0.00%) 
Nervous system disorders         
Cerebrovascular accident  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Syncope  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Radiculopathy  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Psychiatric disorders         
Depression  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Renal and urinary disorders         
Nephrolithiasis  1  0/132 (0.00%)  0/260 (0.00%)  0/263 (0.00%)  1/260 (0.38%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure  1  0/132 (0.00%)  0/260 (0.00%)  1/263 (0.38%)  0/260 (0.00%) 
Vascular disorders         
Peripheral vascular disorder  1  0/132 (0.00%)  1/260 (0.38%)  0/263 (0.00%)  0/260 (0.00%) 
Peripheral artery stenosis  1  0/132 (0.00%)  0/260 (0.00%)  0/263 (0.00%)  1/260 (0.38%) 
Hypertension  1  0/132 (0.00%)  0/260 (0.00%)  0/263 (0.00%)  1/260 (0.38%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
[1]
One treatment-emergent death occurred during treatment with sitagliptin and is not related.
[2]
One treatment-emergent death occurred during treatment with placebo and is not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Sitagliptin 100 mg Fasiglifam 25 mg Fasiglifam 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/132 (12.88%)   16/260 (6.15%)   18/263 (6.84%)   20/260 (7.69%) 
Infections and infestations         
Nasopharyngitis  1  3/132 (2.27%)  8/260 (3.08%)  7/263 (2.66%)  14/260 (5.38%) 
Metabolism and nutrition disorders         
Hyperglycaemia  1  14/132 (10.61%)  9/260 (3.46%)  11/263 (4.18%)  7/260 (2.69%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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 first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Medical Director, Clinical Science
Organization: Takeda
Phone: +1-877-825-3327
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) )
First Submitted: March 6, 2012
First Posted: March 9, 2012
Results First Submitted: March 25, 2015
Results First Posted: June 2, 2016
Last Update Posted: June 2, 2016