Trial Outcomes & Findings for Comparison of TAK-875 (Fasiglifam) With Placebo in Participants With Type 2 Diabetes (NCT NCT01456195)

Last Updated: 2016-04-05

Results Overview

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 with treatment, country, 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 was used for analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

421 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2016-04-05

Participant Flow

Participants took part in the study at 109 investigative sites in United States, Bulgaria, Argentina, Ukraine, Guatemala, Slovakia, Mexico and Hungary from 02 November 2011 to 30 July 2013.

Participants with a diagnosis of Type 2 Diabetes Mellitis were enrolled equally in 1 of 3 treatment groups, once a day placebo, 25 mg fasiglifam or 50 mg fasiglifam.

Participant milestones

Participant milestones
Measure	Placebo Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Overall Study STARTED	143	137	141
Overall Study COMPLETED	132	127	127
Overall Study NOT COMPLETED	11	10	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Overall Study Pretreatment Event/Adverse Event	1	4	1
Overall Study Lost to Follow-up	3	1	3
Overall Study Voluntary Withdrawal	5	3	7
Overall Study Lack of Efficacy	0	1	0
Overall Study Other Reasons	2	1	3

Baseline Characteristics

Comparison of TAK-875 (Fasiglifam) With Placebo in Participants With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=143 Participants Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg n=137 Participants Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg n=141 Participants Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.	Total n=421 Participants Total of all reporting groups
Age, Continuous	53.1 years STANDARD_DEVIATION 10.61 • n=99 Participants	53.2 years STANDARD_DEVIATION 11.31 • n=107 Participants	54.2 years STANDARD_DEVIATION 10.57 • n=206 Participants	53.5 years STANDARD_DEVIATION 10.82 • n=7 Participants
Age, Customized < 65 years	124 participants n=99 Participants	114 participants n=107 Participants	114 participants n=206 Participants	352 participants n=7 Participants
Age, Customized ≥ 65 years	19 participants n=99 Participants	23 participants n=107 Participants	27 participants n=206 Participants	69 participants n=7 Participants
Sex: Female, Male Female	68 Participants n=99 Participants	65 Participants n=107 Participants	73 Participants n=206 Participants	206 Participants n=7 Participants
Sex: Female, Male Male	75 Participants n=99 Participants	72 Participants n=107 Participants	68 Participants n=206 Participants	215 Participants n=7 Participants
Race/Ethnicity, Customized Hispanic or Latino	22 participants n=99 Participants	25 participants n=107 Participants	22 participants n=206 Participants	69 participants n=7 Participants
Race/Ethnicity, Customized Non-Hispanic or Latino	39 participants n=99 Participants	36 participants n=107 Participants	41 participants n=206 Participants	116 participants n=7 Participants
Race/Ethnicity, Customized Not Applicable	82 participants n=99 Participants	76 participants n=107 Participants	78 participants n=206 Participants	236 participants n=7 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	19 participants n=99 Participants	15 participants n=107 Participants	16 participants n=206 Participants	50 participants n=7 Participants
Race/Ethnicity, Customized Asian	5 participants n=99 Participants	4 participants n=107 Participants	0 participants n=206 Participants	9 participants n=7 Participants
Race/Ethnicity, Customized Black or African American	8 participants n=99 Participants	6 participants n=107 Participants	12 participants n=206 Participants	26 participants n=7 Participants
Race/Ethnicity, Customized White	110 participants n=99 Participants	112 participants n=107 Participants	113 participants n=206 Participants	335 participants n=7 Participants
Race/Ethnicity, Customized Multiracial	1 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants	1 participants n=7 Participants
Region of Enrollment Argentina	10 participants n=99 Participants	10 participants n=107 Participants	10 participants n=206 Participants	30 participants n=7 Participants
Region of Enrollment Bulgaria	8 participants n=99 Participants	7 participants n=107 Participants	9 participants n=206 Participants	24 participants n=7 Participants
Region of Enrollment Guatemala	15 participants n=99 Participants	14 participants n=107 Participants	13 participants n=206 Participants	42 participants n=7 Participants
Region of Enrollment Hungary	8 participants n=99 Participants	7 participants n=107 Participants	8 participants n=206 Participants	23 participants n=7 Participants
Region of Enrollment Mexico	6 participants n=99 Participants	5 participants n=107 Participants	7 participants n=206 Participants	18 participants n=7 Participants
Region of Enrollment Slovakia	24 participants n=99 Participants	24 participants n=107 Participants	24 participants n=206 Participants	72 participants n=7 Participants
Region of Enrollment Ukraine	11 participants n=99 Participants	9 participants n=107 Participants	8 participants n=206 Participants	28 participants n=7 Participants
Region of Enrollment United States	61 participants n=99 Participants	61 participants n=107 Participants	62 participants n=206 Participants	184 participants n=7 Participants
Height	166.3 cm STANDARD_DEVIATION 10.63 • n=99 Participants	165.3 cm STANDARD_DEVIATION 11.17 • n=107 Participants	166.7 cm STANDARD_DEVIATION 11.11 • n=206 Participants	166.1 cm STANDARD_DEVIATION 10.96 • n=7 Participants
Weight	89.66 kg STANDARD_DEVIATION 18.858 • n=99 Participants	89.24 kg STANDARD_DEVIATION 18.541 • n=107 Participants	89.43 kg STANDARD_DEVIATION 18.706 • n=206 Participants	89.45 kg STANDARD_DEVIATION 18.660 • n=7 Participants
Baseline Body Mass Index (BMI)	32.33 kg/m^2 STANDARD_DEVIATION 5.714 • n=99 Participants	32.50 kg/m^2 STANDARD_DEVIATION 5.256 • n=107 Participants	32.05 kg/m^2 STANDARD_DEVIATION 5.369 • n=206 Participants	32.29 kg/m^2 STANDARD_DEVIATION 5.443 • n=7 Participants
Baseline BMI Group < 30 kg/m^2	54 participants n=99 Participants	49 participants n=107 Participants	56 participants n=206 Participants	159 participants n=7 Participants
Baseline BMI Group ≥ 30 kg/m^2	89 participants n=99 Participants	88 participants n=107 Participants	85 participants n=206 Participants	262 participants n=7 Participants
Baseline HbA1c Category < 8.5%	102 participants n=99 Participants	91 participants n=107 Participants	102 participants n=206 Participants	295 participants n=7 Participants
Baseline HbA1c Category ≥ 8.5 %	41 participants n=99 Participants	46 participants n=107 Participants	39 participants n=206 Participants	126 participants n=7 Participants
Smoking Classification Never smoked	99 participants n=99 Participants	98 participants n=107 Participants	97 participants n=206 Participants	294 participants n=7 Participants
Smoking Classification Current smoker	21 participants n=99 Participants	17 participants n=107 Participants	23 participants n=206 Participants	61 participants n=7 Participants
Smoking Classification Ex-smoker	23 participants n=99 Participants	22 participants n=107 Participants	21 participants n=206 Participants	66 participants n=7 Participants
Duration of Diabetes	3.048 years STANDARD_DEVIATION 3.164 • n=99 Participants	3.290 years STANDARD_DEVIATION 3.447 • n=107 Participants	3.700 years STANDARD_DEVIATION 4.560 • n=206 Participants	3.345 years STANDARD_DEVIATION 3.773 • n=7 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with data available for analysis. Only participants with Baseline and at least 1 post-Baseline value are included.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg n=119 Participants Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg n=116 Participants Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	-0.17 percent Standard Error 0.090	-0.65 percent Standard Error 0.087	-0.93 percent Standard Error 0.087

SECONDARY outcome

Timeframe: Week 24

The incidence (percentage of participants with) HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) of less than seven percent for target glycemic control at Week 24.

Outcome measures

Outcome measures
Measure	Placebo n=137 Participants Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg n=136 Participants Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg n=139 Participants Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Incidence of HbA1c <7%	24.1 percentage of participants	36.0 percentage of participants	50.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

The change between the fasting plasma glucose value collected at Week 24 relative to Baseline measured in milligrams per deciliter (mg/dL). A MMRM model with treatment, country, 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 was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg n=116 Participants Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg n=116 Participants Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in Fasting Plasma Glucose	1.4 mg/dL Standard Error 3.45	-12.3 mg/dL Standard Error 3.29	-20.9 mg/dL Standard Error 3.26

SECONDARY outcome

Timeframe: Baseline and Week 24

The change between the value of glucose after a meal, measured by the meal tolerance test collected at Week 24 relative to Baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and 2 hours after the start of the meal measured in millimoles per liter (mmol/L). An Analysis of Covariance (ANCOVA) model with treatment and country as fixed factors and Baseline value as covariate was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg n=20 Participants Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg n=18 Participants Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Meal Tolerance Test (MTT)	-0.6 mmol/L Standard Error 12.47	-29.4 mmol/L Standard Error 11.82	-30.6 mmol/L Standard Error 12.50

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Fasiglifam 25 mg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Fasiglifam 50 mg

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=143 participants at risk Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg n=137 participants at risk Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg n=141 participants at risk Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.71% 1/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Gastrointestinal disorders Abdominal hernia	0.00% 0/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.73% 1/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Gastrointestinal disorders Anal fistula	0.00% 0/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.71% 1/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Gastrointestinal disorders Haematochezia	0.00% 0/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.73% 1/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Hepatobiliary disorders Cholecystitis	0.70% 1/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.71% 1/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Hepatobiliary disorders Cholelithiasis	0.70% 1/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Infections and infestations Pneumonia	0.00% 0/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.73% 1/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.
Renal and urinary disorders Renal failure acute	0.70% 1/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.00% 0/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	0.71% 1/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.

Other adverse events

Other adverse events
Measure	Placebo n=143 participants at risk Fasiglifam placebo-matching tablets, orally, once daily for up to 24 weeks.	Fasiglifam 25 mg n=137 participants at risk Fasiglifam 25 mg, tablets, orally, once daily for up to 24 weeks.	Fasiglifam 50 mg n=141 participants at risk Fasiglifam 50 mg, tablets, orally, once daily for up to 24 weeks.
Infections and infestations Nasopharyngitis	6.3% 9/143 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	4.4% 6/137 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.	5.0% 7/141 • First dose of study drug to 30 days past last dose of study drug (Up to 28 Weeks) 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.

Additional Information

Medical Director, Clinical Science

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER