Trial Outcomes & Findings for Study of TAK-875 in Adults With Type 2 Diabetes and Cardiovascular Disease or Risk Factors for Cardiovascular Disease (NCT NCT01609582)

Last Updated: 2015-10-19

Results Overview

The time from randomization to the first occurrences of any event in the primary MACE composite was evaluated using Kaplan-Meier analysis. The primary MACE composite comprised cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for unstable angina (with or without revascularization).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

3207 participants

Primary outcome timeframe

Baseline up to end of study (up to Day 588)

Results posted on

2015-10-19

Participant Flow

Participants took part in the study at 469 investigative sites in 31 countries; 192 sites in North America, 175 in the Europe, Middle East, and Africa (EMEA) region (including Russia, Ukraine, Israel, and South Africa), 65 in the Asia Pacific region, and 37 in Latin/South America from 01 June 2012 to 05 May 2014.

Participants with a historical diagnosis of type 2 diabetes mellitus (T2DM) and clinically-evident cardiovascular (CV) disease or multiple risk factors for CV events who were inadequately controlled while receiving the standard of care were enrolled in 1 of 2 treatment groups: placebo; fasiglifam 50 milligram (mg).

Participant milestones

Participant milestones
Measure	Placebo Fasiglifam placebo-matching tablet, orally, once daily for up to 588 days.	Fasiglifam 50 mg Fasiglifam 50 mg, tablet, orally, once daily for up to 582 days.
Overall Study STARTED	1603	1604
Overall Study Treated	1603	1601
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1603	1604

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Fasiglifam placebo-matching tablet, orally, once daily for up to 588 days.	Fasiglifam 50 mg Fasiglifam 50 mg, tablet, orally, once daily for up to 582 days.
Overall Study Adverse Event	20	18
Overall Study Lost to Follow-up	10	10
Overall Study Withdrawal by Subject	21	15
Overall Study Study Terminated by Sponsor	1543	1548
Overall Study Other	9	10
Overall Study Randomized, but not treated	0	3

Baseline Characteristics

Study of TAK-875 in Adults With Type 2 Diabetes and Cardiovascular Disease or Risk Factors for Cardiovascular Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=1603 Participants Fasiglifam placebo-matching tablet, orally, once daily for up to 588 days.	Fasiglifam 50 mg n=1604 Participants Fasiglifam 50 mg, tablet, orally, once daily for up to 582 days.	Total n=3207 Participants Total of all reporting groups
Age, Continuous	63.9 years STANDARD_DEVIATION 9.03 • n=5 Participants	63.4 years STANDARD_DEVIATION 9.20 • n=7 Participants	63.7 years STANDARD_DEVIATION 9.12 • n=5 Participants
Age, Customized Less than (<) 65 years	794 participants n=5 Participants	851 participants n=7 Participants	1645 participants n=5 Participants
Age, Customized Greater than or equal to (>=) 65 years	809 participants n=5 Participants	753 participants n=7 Participants	1562 participants n=5 Participants
Sex: Female, Male Female	543 Participants n=5 Participants	563 Participants n=7 Participants	1106 Participants n=5 Participants
Sex: Female, Male Male	1060 Participants n=5 Participants	1041 Participants n=7 Participants	2101 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	150 Participants n=5 Participants	119 Participants n=7 Participants	269 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	446 Participants n=5 Participants	477 Participants n=7 Participants	923 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1007 Participants n=5 Participants	1008 Participants n=7 Participants	2015 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	47 participants n=5 Participants	41 participants n=7 Participants	88 participants n=5 Participants
Race/Ethnicity, Customized Asian	199 participants n=5 Participants	205 participants n=7 Participants	404 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	79 participants n=5 Participants	95 participants n=7 Participants	174 participants n=5 Participants
Race/Ethnicity, Customized White	1265 participants n=5 Participants	1246 participants n=7 Participants	2511 participants n=5 Participants
Race/Ethnicity, Customized Multiracial/More than 1 race	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Height	168.1 centimeter (cm) STANDARD_DEVIATION 9.84 • n=5 Participants	167.6 centimeter (cm) STANDARD_DEVIATION 10.54 • n=7 Participants	167.8 centimeter (cm) STANDARD_DEVIATION 10.20 • n=5 Participants
Weight	91.14 kilogram (kg) STANDARD_DEVIATION 19.832 • n=5 Participants	91.40 kilogram (kg) STANDARD_DEVIATION 21.319 • n=7 Participants	91.27 kilogram (kg) STANDARD_DEVIATION 20.586 • n=5 Participants
Body Mass Index (BMI)	32.14 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.107 • n=5 Participants	32.45 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 7.497 • n=7 Participants	32.30 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.838 • n=5 Participants
Glycosylated Hemoglobin (HbA1c) Category <8.5 percent (%)	988 participants n=5 Participants	936 participants n=7 Participants	1924 participants n=5 Participants
Glycosylated Hemoglobin (HbA1c) Category >=8.5%	615 participants n=5 Participants	668 participants n=7 Participants	1283 participants n=5 Participants
Smoking Classification Never smoked	667 participants n=5 Participants	668 participants n=7 Participants	1335 participants n=5 Participants
Smoking Classification Current smoker	330 participants n=5 Participants	328 participants n=7 Participants	658 participants n=5 Participants
Smoking Classification Ex-smoker	606 participants n=5 Participants	608 participants n=7 Participants	1214 participants n=5 Participants
Duration of Diabetes	13.583 years STANDARD_DEVIATION 8.409 • n=5 Participants	13.333 years STANDARD_DEVIATION 8.321 • n=7 Participants	13.458 years STANDARD_DEVIATION 8.365 • n=5 Participants
Region of Enrollment Argentina	121 participants n=5 Participants	121 participants n=7 Participants	242 participants n=5 Participants
Region of Enrollment Australia	34 participants n=5 Participants	35 participants n=7 Participants	69 participants n=5 Participants
Region of Enrollment Bulgaria	21 participants n=5 Participants	22 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment Canada	104 participants n=5 Participants	107 participants n=7 Participants	211 participants n=5 Participants
Region of Enrollment Croatia	16 participants n=5 Participants	17 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment Czech Republic	56 participants n=5 Participants	56 participants n=7 Participants	112 participants n=5 Participants
Region of Enrollment Estonia	13 participants n=5 Participants	11 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment France	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Germany	30 participants n=5 Participants	30 participants n=7 Participants	60 participants n=5 Participants
Region of Enrollment Hong Kong	29 participants n=5 Participants	29 participants n=7 Participants	58 participants n=5 Participants
Region of Enrollment Hungary	74 participants n=5 Participants	72 participants n=7 Participants	146 participants n=5 Participants
Region of Enrollment Israel	25 participants n=5 Participants	26 participants n=7 Participants	51 participants n=5 Participants
Region of Enrollment Italy	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Korea, Republic of	29 participants n=5 Participants	27 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment Latvia	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Lithuania	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment Malaysia	30 participants n=5 Participants	31 participants n=7 Participants	61 participants n=5 Participants
Region of Enrollment Mexico	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants
Region of Enrollment New Zealand	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Peru	18 participants n=5 Participants	17 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment Philippines	25 participants n=5 Participants	24 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment Poland	118 participants n=5 Participants	118 participants n=7 Participants	236 participants n=5 Participants
Region of Enrollment Romania	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Russian Federation	25 participants n=5 Participants	23 participants n=7 Participants	48 participants n=5 Participants
Region of Enrollment Slovakia	31 participants n=5 Participants	31 participants n=7 Participants	62 participants n=5 Participants
Region of Enrollment South Africa	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Taiwan, Province of China	31 participants n=5 Participants	31 participants n=7 Participants	62 participants n=5 Participants
Region of Enrollment Thailand	29 participants n=5 Participants	32 participants n=7 Participants	61 participants n=5 Participants
Region of Enrollment Ukraine	76 participants n=5 Participants	76 participants n=7 Participants	152 participants n=5 Participants
Region of Enrollment United Kingdom	16 participants n=5 Participants	16 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment United States	559 participants n=5 Participants	559 participants n=7 Participants	1118 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to end of study (up to Day 588)

Population: Full Analysis Set (FAS) included all randomized participants who had baseline and at least 1 post-baseline assessment.

Outcome measures

Outcome measures
Measure	Placebo n=1603 Participants Fasiglifam placebo-matching tablet, orally, once daily for up to 588 days.	Fasiglifam 50 mg n=1604 Participants Fasiglifam 50 mg, tablet, orally, once daily for up to 582 days.
Time to First Occurrence of Any Component of Primary Major Adverse Cardiovascular Event (MACE) Composite	NA days Median time and corresponding 95% confidence interval could not be reached since very low number of participants (\<50%) had event related to any component of primary MACE composite.	NA days Median time and corresponding 95% confidence interval could not be reached since very low number of participants (\<50%) had event related to any component of primary MACE composite.

SECONDARY outcome

Timeframe: Baseline up to end of study (up to Day 588)

Population: Full Analysis Set (FAS) included all randomized participants who had baseline and at least 1 post-baseline assessment.

The time from randomization to the first occurrences of any event in the secondary MACE composite was evaluated using Kaplan-Meier analysis. The secondary MACE composite comprised CV death, nonfatal MI, and nonfatal stroke.

Outcome measures

Outcome measures
Measure	Placebo n=1603 Participants Fasiglifam placebo-matching tablet, orally, once daily for up to 588 days.	Fasiglifam 50 mg n=1604 Participants Fasiglifam 50 mg, tablet, orally, once daily for up to 582 days.
Time to First Occurrence of Any Component of Secondary Major Adverse Cardiovascular Event (MACE) Composite	NA days Median time and corresponding 95% confidence interval could not be reached since very low number of participants (\<50%) had event related to any component of secondary MACE composite.	NA days Median time and corresponding 95% confidence interval could not be reached since very low number of participants (\<50%) had event related to any component of secondary MACE composite.

Adverse Events

Placebo

Serious events: 197 serious events

Other events: 427 other events

Deaths: 0 deaths

Fasiglifam 50 mg

Serious events: 201 serious events

Other events: 415 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=1603 participants at risk Fasiglifam placebo-matching tablet, orally, once daily for up to 588 days.	Fasiglifam 50 mg n=1601 participants at risk Fasiglifam 50 mg, tablet, orally, once daily for up to 582 days.
Infections and infestations Upper respiratory tract infection	5.4% 87/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	4.7% 75/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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 Bronchitis	2.8% 45/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	3.1% 49/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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 Diarrhoea	3.0% 48/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.7% 44/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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 Urinary tract infection	2.7% 43/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.2% 35/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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 Nasopharyngitis	3.4% 55/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	3.8% 61/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.
Vascular disorders Hypertension	2.5% 40/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.6% 42/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 36/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.6% 41/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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 Influenza	2.3% 37/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.1% 34/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.
Respiratory, thoracic and mediastinal disorders Cough	1.9% 30/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.5% 40/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.
Nervous system disorders Dizziness	1.9% 30/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.4% 39/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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 Nausea	2.2% 35/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.1% 33/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.
Blood and lymphatic system disorders Anaemia	1.6% 26/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.1% 33/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.
Nervous system disorders Headache	2.0% 32/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	2.6% 41/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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 Sinusitis	2.2% 36/1603 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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.	1.4% 22/1601 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug. 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

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