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
Overview
- Phase
- Phase 3
- Intervention
- TAK-875
- Conditions
- Type 2 Diabetes
- Sponsor
- Takeda
- Enrollment
- 3207
- Primary Endpoint
- Time to First Occurrence of Any Component of Primary Major Adverse Cardiovascular Event (MACE) Composite
- Status
- Terminated
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to demonstrate no excess risk of cardiovascular (CV) composite events exists following long term treatment with TAK-875 compared with placebo.
Detailed Description
The drug being tested in this study is called TAK-875. TAK-875 is being tested to treat people who have diabetes. This study will look at the number of cardiovascular events (for example, heart attacks) of people who take TAK-875 in comparison to placebo in addition to standard care. The study will enroll approximately 5000 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * TAK-875 50 mg. * Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient. All participants will be asked to take one tablet at the same time each day throughout the study. All participants will be asked to record any time they have low blood sugar symptoms in a diary. This multi-centre trial will be conducted worldwide, in approximately 700 sites. The overall time to participate in this study is 6 years. Participants will make up to approximately 24 visits to the clinic, with telephone visits conducted on an alternate 6 month schedule starting from Month 27. Due to potential concerns about liver safety, on balance, the benefits of treating patients with fasiglifam (TAK-875) do not outweigh the potential risks. For this reason, Takeda has decided voluntarily to terminate the development activities for fasiglifam.
Investigators
Eligibility Criteria
Inclusion Criteria
- •In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements, including scheduled clinic appointments.
- •The patient or, when applicable, the patient'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.
- •Has a diagnosis of type 2 diabetes mellitus.
- •Has an glycosylated hemoglobin (HbA1c) level between 7.0% and 10.5%, inclusive, at Screening. HbA1c testing may be repeated once during Screening.
- •Meets at least one (1) of the following three (3) High Risk Categories (a-c ):
- •A documented history of myocardial infarction (MI) occurring no less than 2 months (60 days) and no greater than 24 months prior to Screening.
- •Documented symptomatic peripheral arterial disease (PAD) (at least one (1) of the following three (3) criteria must be satisfied): i) Current intermittent claudication together with documented ankle-brachial index ≤0.
- •ii) History of previous vascular intervention for intermittent claudication or resting limb ischemia (example: amputation for arterial disease, peripheral bypass, or history of angioplasty/stenting). iii) History of symptomatic carotid artery disease (requiring revascularization with carotid endarterectomy (CEA) or stenting).
- •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. ii) A history of ischemic stroke (IS) (with a Modified Rankin Scale Score ≤3 documented prior to Randomization) not less than 2 months (60 days) and no greater than 24 months prior to Screening, and clinically and neurologically stable at Randomization. The Modified Rankin Scale is located in appendix in protocol.
- •Or meets at least one (1) of the following five (5) Intermediate Risk Categories (d-h):
Exclusion Criteria
- •Has received any investigational medication within 30 days prior to Screening or any investigational antidiabetic medication or excluded medications within 3 months prior to Screening.
- •Has been randomized into a previous TAK-875 study.
- •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
- •Is diagnosed with type 1 diabetes mellitus or latent autoimmune diabetes in adults.
- •Is hemodynamically unstable, including severe heart failure (New York Heart Association Class IV) at Screening.
- •Is hospitalized at the Screening Visit for the event associated with the CV inclusion criteria. (Patients 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).
- •Has ALT and/or AST levels \>3.0x ULN at Screening.
- •Has a total bilirubin level \>ULN at Screening. Exception: if a patient has documented Gilbert's Syndrome, the patient will be allowed with an elevated bilirubin level per the investigator's discretion.
- •Has an glomerular filtration rate (estimated) (eGFR) ≤ 15 mL/min/1.73m2 based on Modification of Diet in Renal Disease (MDRD) calculation at Screening and is currently on dialysis or expected to start dialysis within the next 6 months.
- •Has uncontrolled thyroid disease, as determined by the investigator and/or clinical investigation.
Arms & Interventions
TAK-875 50 mg
TAK-875 50 mg tablets, orally, once daily for up to 6 years.
Intervention: TAK-875
Placebo
TAK-875 placebo-matching tablets, orally, once daily for up to 6 years.
Intervention: TAK-875 Placebo
Outcomes
Primary Outcomes
Time to First Occurrence of Any Component of Primary Major Adverse Cardiovascular Event (MACE) Composite
Time Frame: Baseline up to end of study (up to Day 588)
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).
Secondary Outcomes
- Time to First Occurrence of Any Component of Secondary Major Adverse Cardiovascular Event (MACE) Composite(Baseline up to end of study (up to Day 588))