Clinical Trials List
Protocol NumberTAK-875_306
2012-11-12 - 2018-12-31
Phase III
Terminated7
ICD-10E11.9
Type 2 diabetes mellitus without complications
ICD-10E13.9
Other specified diabetes mellitus without complications
ICD-9250.00
Diabetes mellitus without mention of complication, Type II [non-insulin dependent type][NIDDM type] [ adult-onset type] or unspecified type, not stated as uncontrolled
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate Cardiovascular Outcomes of TAK-875, 50 mg in Addition to Standard of Care in Subjects with Type 2 Diabetes and with Cardiovascular Disease or Multiple Risk Factors for Cardiovascular Events
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Takeda Global Research and Development Center (Asia) Pte. Ltd
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wen-Chung Yu Division of Cardiovascular Diseases
- Chin-Sung Kuo Division of Endocrinology
- Shih-Hsien Sung Division of Cardiovascular Diseases
- Tse-Min Lu Division of Cardiovascular Diseases
- Kang-Ling Wang Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Principal Investigator
Co-Principal Investigator
- JUN-SING WANG Division of Endocrinology
- 蘇碩偉 Division of Endocrinology
- 黃怡文 Division of Endocrinology
- 林時逸 Division of Endocrinology
- 蔡婉妮 Division of Endocrinology
- 李佳霖 Division of Endocrinology
- 許惠恒 Division of Endocrinology
- 傅家保 Division of Endocrinology
- 陳拓邦 Division of Endocrinology
- I-TE LEE Division of Endocrinology
- 張心玫 Division of Endocrinology
- 李昂澤 Division of Endocrinology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 方修御 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 徐國基 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 謝禮全 Division of Cardiovascular Diseases
- 王子源 Division of Endocrinology
- Po-Yen Ko Division of Cardiovascular Diseases
- 盧炯睿 Division of Cardiovascular Diseases
- 陳業鵬 Division of Cardiovascular Diseases
- Shih-Sheng Chang Division of Cardiovascular Diseases
- Ping-Han Lo Division of Cardiovascular Diseases
- 楊晨佳 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Type 2 Diabete
Objectives
The primary objective is to demonstrate that no excess risk of CV composite events exists following treatment with TAK-875 compared with placebo when given in combination with Standard of Care in subjects with T2DM and clinically evident CV disease or multiple risk factors for CV events. For purposes of this study, the primary MACE composite comprises CV death, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for unstable
angina (with or without revascularization)
Test Drug
TAK-875
Active Ingredient
TAK-875
Dosage Form
Tablet
Dosage
50 mg
Endpoints
The time from randomization to each of the components of the primary composite MACE
endpoint:
– CV death.
– Nonfatal MI.
– Nonfatal stroke.
– Hospitalization for unstable angina (with or without revascularization).
– The time from randomization to the first event for each of the following:
All-cause mortality
Hospitalization for heart failure.
Metabolic efficacy endpoints will include the following:
– Change from baseline in HbA1c at Months 1, 3, 6, 9, 12, 16, 20, 24 and every 6 months
until end of study.
– Change from baseline in FPG at Months 1, 3, 6, 9, 12, 16, 20, 24 and every 6 months until
end of study.
– Change from baseline in highly selective C-reactive protein (hs-CRP) at Month 12 and
every 12 months until end of study.
– Change from baseline in serum lipids, including triglycerides, total cholesterol,
high-density lipoprotein (HDL), and low-density lipoprotein (LDL), at Months 1, 3, 6, 9,
12, 16, 20, 24 and every 6 months until end of study.
Safety endpoints will include the following:
– Incidence of adverse events (AEs)/SAEs.
– Incidence of hypoglycemia: number of subjects and number of events overall as well as by
the following subcategories:
Severe hypoglycemia: An event requiring assistance of another person to actively
administer carbohydrate, glucagon, or other resuscitative actions. Blood glucose may
not be available.
Documented symptomatic hypoglycemia: Typical symptoms of hypoglycemia
accompanied by blood glucose 70 mg/dL (3.9 mmol/L).
Asymptomatic hypoglycemia: Blood glucose 70 mg/dL (3.9 mmol/L), but with no
typical symptoms.
Probable symptomatic hypoglycemia: Symptoms of hypoglycemia that are not
accompanied by blood glucose determination 70 mg/dL (3.9 mmol/L).
Relative hypoglycemia: Symptoms of hypoglycemia, but with a measured blood
glucose >70 mg/dL (3.9 mmol/L).
Additional subcategory: Blood glucose 55 mg/dL with or without symptoms of
hypoglycemia.
– Liver function.
Changes from baseline in serum liver function tests, including incidence of markedly
abnormal values.
– Renal function.
Changes from baseline in serum creatinine and estimated glomerular filtration rate
(eGFR), including the incidence of markedly abnormal values.
Incidence of renal dialysis.
Incidence of kidney transplant.
– Electrocardiograms (ECGs).
– Vital sign measurements (blood pressure and heart rate) and body weight.
– Clinical laboratory evaluations (hematology, serum chemistry, and urinalysis).
Additional endpoints will include the following:
– Change from baseline of patient reported outcomes on EQ-5D with VAS, D-ABS and
D-MIQ at Months 3, 6, 12, 20, 24 and every 6 months until end of study as well as D-ABS
at Month 1, as well as patient reported outcomes on the Healthcare Resource Utilization
Diary.
– Mean use of diabetes control-related healthcare resources for each treatment group for the
following categories: medications, emergency room visits, days in hospital, visits to
physicians and other health professionals, tests/procedures, time off work, and unpaid supportive care
endpoint:
– CV death.
– Nonfatal MI.
– Nonfatal stroke.
– Hospitalization for unstable angina (with or without revascularization).
– The time from randomization to the first event for each of the following:
All-cause mortality
Hospitalization for heart failure.
Metabolic efficacy endpoints will include the following:
– Change from baseline in HbA1c at Months 1, 3, 6, 9, 12, 16, 20, 24 and every 6 months
until end of study.
– Change from baseline in FPG at Months 1, 3, 6, 9, 12, 16, 20, 24 and every 6 months until
end of study.
– Change from baseline in highly selective C-reactive protein (hs-CRP) at Month 12 and
every 12 months until end of study.
– Change from baseline in serum lipids, including triglycerides, total cholesterol,
high-density lipoprotein (HDL), and low-density lipoprotein (LDL), at Months 1, 3, 6, 9,
12, 16, 20, 24 and every 6 months until end of study.
Safety endpoints will include the following:
– Incidence of adverse events (AEs)/SAEs.
– Incidence of hypoglycemia: number of subjects and number of events overall as well as by
the following subcategories:
Severe hypoglycemia: An event requiring assistance of another person to actively
administer carbohydrate, glucagon, or other resuscitative actions. Blood glucose may
not be available.
Documented symptomatic hypoglycemia: Typical symptoms of hypoglycemia
accompanied by blood glucose 70 mg/dL (3.9 mmol/L).
Asymptomatic hypoglycemia: Blood glucose 70 mg/dL (3.9 mmol/L), but with no
typical symptoms.
Probable symptomatic hypoglycemia: Symptoms of hypoglycemia that are not
accompanied by blood glucose determination 70 mg/dL (3.9 mmol/L).
Relative hypoglycemia: Symptoms of hypoglycemia, but with a measured blood
glucose >70 mg/dL (3.9 mmol/L).
Additional subcategory: Blood glucose 55 mg/dL with or without symptoms of
hypoglycemia.
– Liver function.
Changes from baseline in serum liver function tests, including incidence of markedly
abnormal values.
– Renal function.
Changes from baseline in serum creatinine and estimated glomerular filtration rate
(eGFR), including the incidence of markedly abnormal values.
Incidence of renal dialysis.
Incidence of kidney transplant.
– Electrocardiograms (ECGs).
– Vital sign measurements (blood pressure and heart rate) and body weight.
– Clinical laboratory evaluations (hematology, serum chemistry, and urinalysis).
Additional endpoints will include the following:
– Change from baseline of patient reported outcomes on EQ-5D with VAS, D-ABS and
D-MIQ at Months 3, 6, 12, 20, 24 and every 6 months until end of study as well as D-ABS
at Month 1, as well as patient reported outcomes on the Healthcare Resource Utilization
Diary.
– Mean use of diabetes control-related healthcare resources for each treatment group for the
following categories: medications, emergency room visits, days in hospital, visits to
physicians and other health professionals, tests/procedures, time off work, and unpaid supportive care
Inclution Criteria
Inclusion Criteria
Subject eligibility is determined according to the following criteria:
1. In the opinion of the investigator, the subject is capable of understanding and complying with
protocol requirements, including scheduled clinic appointments.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates
a written, informed consent form and any required privacy authorization prior to the initiation
of any study procedures.
3. The subject is male or female and 18 years of age or older.
4. The subject has a diagnosis of T2DM.
5. The subject has an HbA1c level between 7.0% and 10.5%, inclusive, at Screening. HbA1c testing may be repeated once during Screening.
6. The subject meets at least one (1) of the following three (3) High Risk Categories (a-c):
a) A documented history of myocardial infarction (MI) occurring no less than 2 months
(60 days) and no greater than 24 months prior to Screening.
b) Documented symptomatic peripheral arterial disease (PAD) (at least one (1) of the
following three (3) criteria must be satisfied):
a. Current intermittent claudication together with documented ankle-brachial index
≤0.85.
b. History of intermittent claudication or resting limb ischemia together with previous
related vascular intervention (amputation for arterial disease, peripheral bypass, or
history of angioplasty/stenting).
c. History of symptomatic carotid artery disease (requiring revascularization with
carotid endarterectomy (CEA) or stenting).
c) Documented cerebrovascular disease (at least one (1) of the following two (2) criteria
must be satisfied):
i. A history of transient ischemic attack (TIA) confirmed by a neurologist no greater
than 24 months prior to screening and clinically and neurologically stable at
randomization.
Subject eligibility is determined according to the following criteria:
1. In the opinion of the investigator, the subject is capable of understanding and complying with
protocol requirements, including scheduled clinic appointments.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates
a written, informed consent form and any required privacy authorization prior to the initiation
of any study procedures.
3. The subject is male or female and 18 years of age or older.
4. The subject has a diagnosis of T2DM.
5. The subject has an HbA1c level between 7.0% and 10.5%, inclusive, at Screening. HbA1c testing may be repeated once during Screening.
6. The subject meets at least one (1) of the following three (3) High Risk Categories (a-c):
a) A documented history of myocardial infarction (MI) occurring no less than 2 months
(60 days) and no greater than 24 months prior to Screening.
b) Documented symptomatic peripheral arterial disease (PAD) (at least one (1) of the
following three (3) criteria must be satisfied):
a. Current intermittent claudication together with documented ankle-brachial index
≤0.85.
b. History of intermittent claudication or resting limb ischemia together with previous
related vascular intervention (amputation for arterial disease, peripheral bypass, or
history of angioplasty/stenting).
c. History of symptomatic carotid artery disease (requiring revascularization with
carotid endarterectomy (CEA) or stenting).
c) Documented cerebrovascular disease (at least one (1) of the following two (2) criteria
must be satisfied):
i. A history of transient ischemic attack (TIA) confirmed by a neurologist no greater
than 24 months prior to screening and clinically and neurologically stable at
randomization.
Exclusion Criteria
Exclusion Criteria
Any subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject has received any investigational medication within 30 days prior to Screening or
any investigational antidiabetic medication or excluded medications listed in Section 7.3
within 3 months prior to Screening.
2. The subject has been randomized into a previous TAK-875 study.
3. The subject is an immediate family member, study site employee, or is in a dependant
relationship with a study site employee who is involved in conduct of this study (eg, spouse,
parent, biological or legally adopted child, or sibling) or may consent under duress
4. The subject is diagnosed with type 1 diabetes mellitus or latent autoimmune diabetes in adults.
5. The subject is hemodynamically unstable, including severe heart failure (New York Heart
Association Class IV) at Screening.
6. The subject is hospitalized at the Screening Visit for the event associated with the CV inclusion
criteria. (Subjects who have been discharged from an acute hospital to a cardiac rehabilitation
center or nursing home at the time of the Screening Visit or Randomization Visit are not
excluded).
7. The subject has ALT and/or aspartate aminotransferase (AST) levels >3.0x ULN at Screening.
8. The subject has a total bilirubin level >ULN at Screening. Exception: if a subject has
documented Gilbert’s Syndrome, the subject will be allowed with an elevated bilirubin level
per the investigator’s discretion.
9. The subject has an eGFR ≤ 15 mL/min/1.73m2
based on Modification of Diet in Renal Disease
(MDRD) calculation at Screening and is not currently or expected to start dialysis within the
next 6 months.
10. The subject has uncontrolled thyroid disease.
11. The subject has a known history of infection with human immunodeficiency virus (HIV).
12. The subject has a known history of active infection with Hepatitis B virus (HBV), or Hepatitis
C virus (HCV) requiring antiviral treatment.
13. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse
within 2 years prior to Screening.
14. The subject has any major illness or condition that, in the investigator’s opinion, prohibits the
subject from participating in the study or meeting planned visit schedule.
15. The subject has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to TAK-875.
16. If female, the subject is pregnant (confirmed by laboratory testing, ie, serum or urine human chorionic gonadotropin (hCG), in females of childbearing potential) or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or
intending to donate ova during such time period.
17. The subject is unable to understand verbal or written English or any other language for which a
certified translation of the approved informed consent is available.
18. The subject has a history of cancer that has been in remission for <5 years prior to Screening. A
history of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin is allowed.
Any subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject has received any investigational medication within 30 days prior to Screening or
any investigational antidiabetic medication or excluded medications listed in Section 7.3
within 3 months prior to Screening.
2. The subject has been randomized into a previous TAK-875 study.
3. The subject is an immediate family member, study site employee, or is in a dependant
relationship with a study site employee who is involved in conduct of this study (eg, spouse,
parent, biological or legally adopted child, or sibling) or may consent under duress
4. The subject is diagnosed with type 1 diabetes mellitus or latent autoimmune diabetes in adults.
5. The subject is hemodynamically unstable, including severe heart failure (New York Heart
Association Class IV) at Screening.
6. The subject is hospitalized at the Screening Visit for the event associated with the CV inclusion
criteria. (Subjects who have been discharged from an acute hospital to a cardiac rehabilitation
center or nursing home at the time of the Screening Visit or Randomization Visit are not
excluded).
7. The subject has ALT and/or aspartate aminotransferase (AST) levels >3.0x ULN at Screening.
8. The subject has a total bilirubin level >ULN at Screening. Exception: if a subject has
documented Gilbert’s Syndrome, the subject will be allowed with an elevated bilirubin level
per the investigator’s discretion.
9. The subject has an eGFR ≤ 15 mL/min/1.73m2
based on Modification of Diet in Renal Disease
(MDRD) calculation at Screening and is not currently or expected to start dialysis within the
next 6 months.
10. The subject has uncontrolled thyroid disease.
11. The subject has a known history of infection with human immunodeficiency virus (HIV).
12. The subject has a known history of active infection with Hepatitis B virus (HBV), or Hepatitis
C virus (HCV) requiring antiviral treatment.
13. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse
within 2 years prior to Screening.
14. The subject has any major illness or condition that, in the investigator’s opinion, prohibits the
subject from participating in the study or meeting planned visit schedule.
15. The subject has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to TAK-875.
16. If female, the subject is pregnant (confirmed by laboratory testing, ie, serum or urine human chorionic gonadotropin (hCG), in females of childbearing potential) or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or
intending to donate ova during such time period.
17. The subject is unable to understand verbal or written English or any other language for which a
certified translation of the approved informed consent is available.
18. The subject has a history of cancer that has been in remission for <5 years prior to Screening. A
history of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin is allowed.
The Estimated Number of Participants
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Taiwan
85 participants
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Global
5000 participants
