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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Disease; Type 2 Diabetes
• Intervention / Treatment: Drug: TAK-875; Drug: TAK-875 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.

• Study Type: Interventional
• Enrollment (Actual): 3207
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina
  • Cordoba, Argentina
  • Corrientes, Argentina
  • Mendoza, Argentina
  • Rosario, Argentina
  • Salta, Argentina
  • Santa Fe, Argentina
  • Santiago del estero, Argentina
  • Buenos Aires
    • Bahia Blanca, Buenos Aires, Argentina
    • Haedo, Buenos Aires, Argentina
    • La Plata, Buenos Aires, Argentina
    • Loma Hermosa, Buenos Aires, Argentina
    • Mar del Plata, Buenos Aires, Argentina
    • Quilmes, Buenos Aires, Argentina
    • San Nicolas, Buenos Aires, Argentina
    • Zarate, Buenos Aires, Argentina
  • Chubut
    • Trelew, Chubut, Argentina
  • Ciudad Autonoma Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina
  • Cordoba
    • Córdoba, Cordoba, Argentina
    • Villa Cabrera, Cordoba, Argentina
    • Villa Maria, Cordoba, Argentina
  • Jujy
    • San Salvador de Jujuy, Jujy, Argentina
  • Mendoza
    • Godoy Cruz, Mendoza, Argentina
  • Rio Negro
    • Cipolletti, Rio Negro, Argentina
  • Santa Fe
    • Rosario, Santa Fe, Argentina
    • Venado Tuerto, Santa Fe, Argentina
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina
• Australia
  • Bruce, Australia
  • Garran, Australia
  • Australian Capital Territory
    • Bruce, Australian Capital Territory, Australia
    • Canberra, Australian Capital Territory, Australia
    • Garran, Australian Capital Territory, Australia
  • New South Wales
    • Westmead, New South Wales, Australia
    • Wollongong, New South Wales, Australia
  • Queensland
    • Brisbane, Queensland, Australia
    • Meadowbrook, Queensland, Australia
    • Milton, Queensland, Australia
    • Townsville, Queensland, Australia
    • Woolloongabba, Queensland, Australia
  • South Australia
    • Adelaide, South Australia, Australia
    • Daw Park, South Australia, Australia
    • Elizabeth Vale, South Australia, Australia
  • Victoria
    • Clayton, Victoria, Australia
    • Fitzroy, Victoria, Australia
    • Geelong, Victoria, Australia
    • Melbourne, Victoria, Australia
    • Sale, Victoria, Australia
  • Western Australia
    • Joondalup, Western Australia, Australia
• Brazil
  • Sao Paulo, Brazil
  • Ceará
    • Fortaleza, Ceará, Brazil
  • Distrito Federal
    • Brasilia, Distrito Federal, Brazil
  • Goiás
    • Goiania, Goiás, Brazil
  • Paraná
    • Campina Grande do Sul, Paraná, Brazil
    • Curitiba, Paraná, Brazil
  • Pará
    • Belem, Pará, Brazil
  • Pernambuco
    • Recife, Pernambuco, Brazil
  • Rio Grande do Sul
    • Canoas, Rio Grande do Sul, Brazil
    • Caxias do Sul, Rio Grande do Sul, Brazil
    • Passo Fundo, Rio Grande do Sul, Brazil
    • Porto Alegre, Rio Grande do Sul, Brazil
    • Santa Maria, Rio Grande do Sul, Brazil
  • Sao Paulo
    • Marilia, Sao Paulo, Brazil
    • São Paulo, Sao Paulo, Brazil
• Bulgaria
  • Blagoevgrad, Bulgaria
  • Byala, Bulgaria
  • Kazanlak, Bulgaria
  • Pazardzhik, Bulgaria
  • Plovdiv, Bulgaria
  • Sevlievo, Bulgaria
  • Sofia, Bulgaria
  • Stara Zagora, Bulgaria
  • Varna, Bulgaria
• Canada
  • Quebec, Canada
  • Alberta
    • Calgary, Alberta, Canada
    • Spruce Grove, Alberta, Canada
  • British Columbia
    • Victoria, British Columbia, Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
  • Ontario
    • Brampton, Ontario, Canada
    • Etobicoke, Ontario, Canada
    • Hamilton, Ontario, Canada
    • Markham, Ontario, Canada
    • Oakville, Ontario, Canada
    • Ottawa, Ontario, Canada
    • Sudbury, Ontario, Canada
    • Thornhill, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Gatineau, Quebec, Canada
    • Laval, Quebec, Canada
    • Longueuil, Quebec, Canada
    • Montreal, Quebec, Canada
    • Pointe Claire, Quebec, Canada
    • St-Jérôme, Quebec, Canada
    • Ville Saint-Laurent, Quebec, Canada
• Croatia
  • Cakovec, Croatia
  • Karlovac, Croatia
  • Koprivnica, Croatia
  • Krapinske Toplice, Croatia
  • Osijek, Croatia
  • Rijeka, Croatia
  • Sisak, Croatia
  • Slavonski Brod, Croatia
  • Split, Croatia
  • Virovitica, Croatia
  • Zadar, Croatia
  • Zagreb, Croatia
• Czech Republic
  • Ceske Budejovice, Czech Republic
  • Chocen, Czech Republic
  • Jindrichuv Hradec, Czech Republic
  • Kromeriz, Czech Republic
  • Marianske Lazne, Czech Republic
  • Moravsky Krumlov, Czech Republic
  • Olomouc, Czech Republic
  • Ostrava, Czech Republic
  • Ostrava - Moravska Ostrava, Czech Republic
  • Ostrava - Vitkovice, Czech Republic
  • Prague 10, Czech Republic
  • Praha 4 - Krc, Czech Republic
  • Praha 5, Czech Republic
  • Slany, Czech Republic
  • Trutnov, Czech Republic
  • Usti nad Labem, Czech Republic
• Estonia
  • Paide, Estonia
  • Tallinn, Estonia
  • Tartu, Estonia
• France
  • Paris, France
  • Essonne
    • Corbeil Essonne, Essonne, France
    • Corbeil Essonnes, Essonne, France
  • Gironde
    • Pessac, Gironde, France
  • Hauts de Seine
    • Nanterre cedex, Hauts de Seine, France
  • Loire Atlantique
    • Nantes cedex 01, Loire Atlantique, France
  • Rhone
    • Pierre-Bénite cedex, Rhone, France
• Germany
  • Berlin, Germany
  • Hamburg, Germany
  • Baden Wuerttemberg
    • Friedrichsthal, Baden Wuerttemberg, Germany
  • Brandenburg
    • Falkensee, Brandenburg, Germany
  • Hessen
    • Kelkheim, Hessen, Germany
  • Nordrhein Westfalen
    • Dortmund, Nordrhein Westfalen, Germany
    • Essen, Nordrhein Westfalen, Germany
    • Goch, Nordrhein Westfalen, Germany
    • Kamp-Lintfort, Nordrhein Westfalen, Germany
    • Koeln, Nordrhein Westfalen, Germany
  • Rheinland Pfalz
    • Bad Kreuznach, Rheinland Pfalz, Germany
  • Sachsen
    • Dippoldiswalde, Sachsen, Germany
    • Dresden, Sachsen, Germany
  • Sachsen Anhalt
    • Hohenmoelsen, Sachsen Anhalt, Germany
• Hong Kong
  • Hong Kong, Hong Kong
  • New Territories, Hong Kong
• Hungary
  • Baja, Hungary
  • Balatonfured, Hungary
  • Budaors, Hungary
  • Budapest, Hungary
  • Debrecen, Hungary
  • Eger, Hungary
  • Godollo, Hungary
  • Gyula, Hungary
  • Kecskemet, Hungary
  • Kistelek, Hungary
  • Komarom, Hungary
  • Mako, Hungary
  • Pecs, Hungary
  • Szeged, Hungary
  • Szekszard, Hungary
  • Szikszo, Hungary
  • Szombathely, Hungary
  • Urhida, Hungary
  • Veszprem, Hungary
  • Zalaegerszeg, Hungary
• Israel
  • Ashkelon, Israel
  • Beer Sheva, Israel
  • Beer Yaakov, Israel
  • Beer-Sheva, Israel
  • Givataim, Israel
  • Hadera, Israel
  • Haifa, Israel
  • Holon, Israel
  • Jerusalem, Israel
  • Kfar-Saba, Israel
  • Petach Tikva, Israel
  • Petach Tikwa, Israel
  • Raanana, Israel
  • Tel Aviv, Israel
  • Zefat, Israel
• Italy
  • Firenze, Italy
  • Milano, Italy
  • Pavia, Italy
  • Milano
    • San Donato Milanese, Milano, Italy
    • Sesto San Giovanni, Milano, Italy
• Korea, Republic of
  • Busan, Korea, Republic of
  • Gyeonggi, Korea, Republic of
  • Seoul, Korea, Republic of
  • Gangwon-do
    • Wonju-Si, Gangwon-do, Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
  • Gyeongsangnam-do
    • Yangsan-si, Gyeongsangnam-do, Korea, Republic of
  • Jeollabuk-do
    • Jeonju-si, Jeollabuk-do, Korea, Republic of
• Latvia
  • Daugavpils, Latvia
  • Jelgava, Latvia
  • Limbazi, Latvia
  • Ogre, Latvia
  • Riga, Latvia
  • Talsi, Latvia
  • Valmiera, Latvia
• Lithuania
  • Alytus, Lithuania
  • Kaunas, Lithuania
  • Klaipeda, Lithuania
• Malaysia
  • Kelantan, Malaysia
  • Kuala Lumpur, Malaysia
  • Melaka, Malaysia
  • Selangor, Malaysia
  • Terengganu, Malaysia
  • Johor
    • Johor Bahru, Johor, Malaysia
  • Kedah
    • Alor Setar, Kedah, Malaysia
  • Kelantan
    • Kota Bahru, Kelantan, Malaysia
    • Kota Bharu, Kelantan, Malaysia
  • Kuala Lumpur
    • Lembah Pantai, Kuala Lumpur, Malaysia
  • Perak
    • Ipoh, Perak, Malaysia
    • Taiping, Perak, Malaysia
    • Taiping, Perak, Perak, Malaysia
  • Selangor
    • Petaling Jaya, Selangor, Malaysia
• Mexico
  • Aguascalientes, Mexico
  • Chihuahua, Mexico
  • Durango, Mexico
  • Tamaulipas, Mexico
  • Baja California Norte
    • Tijuana, Baja California Norte, Mexico
  • Coahuila
    • Torreon, Coahuila, Mexico
  • Distrito Federal
    • Cuauhtemoc, Distrito Federal, Mexico
    • Mexico, Distrito Federal, Mexico
  • Estado de Mexico
    • Cuautitlan Izcalli, Estado de Mexico, Mexico
    • Metepec, Estado de Mexico, Mexico
  • Guerrero
    • Acapulco de Juárez, Guerrero, Mexico
  • Hidalgo
    • Pachuca, Hidalgo, Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico
    • Zapopan, Jalisco, Mexico
  • Michoacán
    • Morelia, Michoacán, Mexico
  • Morelos
    • Cuernavaca, Morelos, Mexico
  • Nuevo Le=n
    • Monterrey, Nuevo Le=n, Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico
  • San Luis Potos
    • San Luis Potosi, San Luis Potos, Mexico
  • Sinaloa
    • Culiacan, Sinaloa, Mexico
  • Veracruz
    • Xalapa, Veracruz, Mexico
  • Yucatán
    • Merida, Yucatán, Mexico
• New Zealand
  • Auckland, New Zealand
  • Christchurch, New Zealand
  • Dunedin, New Zealand
  • Palmerston North, New Zealand
  • Tauranga, New Zealand
  • Wellington, New Zealand
• Peru
  • Callao, Peru
  • Cusco, Peru
  • Huacho, Peru
  • Ica, Peru
  • La Libertad, Peru
  • Lima, Peru
  • Piura, Peru
• Philippines
  • Baguio City, Philippines
  • Cebu City, Philippines
  • Dasmariñas City, Cavite, Philippines
  • Davao City, Philippines
  • Iloilo City, Philippines
  • Marikina City, Philippines
  • Quezon City, Philippines
  • Tarlac, Philippines
  • Taytay, Philippines
• Poland
  • Bialystok, Poland
  • Gdansk, Poland
  • Gliwice, Poland
  • Grodzisk Mazowiecki, Poland
  • Kamieniec Zabkowicki, Poland
  • Leczyca, Poland
  • Lodz, Poland
  • Lublin, Poland
  • Oswiecim, Poland
  • Parczew, Poland
  • Poznan, Poland
  • Pulawy, Poland
  • Radom, Poland
  • Ruda Slaska, Poland
  • Rzeszow, Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Romania
  • Bacau, Romania
  • Baia Mare, Romania
  • Brasov, Romania
  • Bucuresti, Romania
  • Galati, Romania
  • Iasi, Romania
  • Oradea, Romania
  • Ploiesti, Romania
  • Targu Mures, Romania
  • Timisoara, Romania
• Russian Federation
  • Arkhangelsk, Russian Federation
  • Barnaul, Russian Federation
  • Kazan, Russian Federation
  • Kemerovo, Russian Federation
  • Moscow, Russian Federation
  • Nizhniy Novgorod, Russian Federation
  • Novosibirsk, Russian Federation
  • Pushkin, Russian Federation
  • Saratov, Russian Federation
  • St. Petersburg, Russian Federation
  • Yaroslavl, Russian Federation
• Slovakia
  • Bratislava, Slovakia
  • Komarno, Slovakia
  • Kosice, Slovakia
  • Levice, Slovakia
  • Lucenec, Slovakia
  • Martin, Slovakia
  • Nitra, Slovakia
  • Nove Mesto nad Vahom, Slovakia
  • Presov, Slovakia
  • Sahy, Slovakia
  • Svidnik, Slovakia
  • Trencin, Slovakia
  • Zilina, Slovakia
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa
  • Free State
    • Bloemfontein, Free State, South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa
    • Kempton Park, Gauteng, South Africa
    • Krugersdorp, Gauteng, South Africa
    • Lenasia, Gauteng, South Africa
    • Pretoria, Gauteng, South Africa
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa
    • Stellenbosch, Western Cape, South Africa
    • Worcester, Western Cape, South Africa
• Taiwan
  • Douliou City, Taiwan
  • Kaohsiung, Taiwan
  • New Taipei City, Taiwan
  • Taichung, Taiwan
  • Tainan, Taiwan
  • Taipei, Taiwan
• Thailand
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand
    • Dusit, Bangkok, Thailand
    • Patumwan, Bangkok, Thailand
    • Rachathevi, Bangkok, Thailand
    • Rajtevi, Bangkok, Thailand
    • Ratchathewi, Bangkok, Thailand
  • Chiang Mai
    • Muang, Chiang Mai, Thailand
  • Chiang Rai
    • Muang, Chiang Rai, Thailand
  • Khon Kaen
    • Muang, Khon Kaen, Thailand
  • Nakhon Ratchasima
    • Muang, Nakhon Ratchasima, Thailand
• Ukraine
  • Donetsk, Ukraine
  • Kharkiv, Ukraine
  • Kyiv, Ukraine
  • Lugansk, Ukraine
  • Mykolayiv, Ukraine
  • Odesa, Ukraine
  • Poltava, Ukraine
  • Simferopol, Ukraine
  • Ternopil, Ukraine
  • Vinnycia, Ukraine
  • Vinnytsia, Ukraine
  • Zaporizhzhia, Ukraine
• United Kingdom
  • Cardiff, United Kingdom
  • Cornwall
    • Truro, Cornwall, United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom
    • Plymouth, Devon, United Kingdom
    • Torquay, Devon, United Kingdom
  • East Riding of Yorkshire
    • Hull, East Riding of Yorkshire, United Kingdom
  • East Sussex
    • Bexhill on Sea, East Sussex, United Kingdom
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom
  • Hertfordshire
    • Watford, Hertfordshire, United Kingdom
  • Kent
    • Gillingham, Kent, United Kingdom
  • Lancashire
    • Thornton-Cleveleys, Lancashire, United Kingdom
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom
  • Merseyside
    • Liverpool, Merseyside, United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom
    • Northwood, Middlesex, United Kingdom
  • Staffordshire
    • Stoke on Trent, Staffordshire, United Kingdom
  • West Glamorgan
    • Swansea, West Glamorgan, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Dothan, Alabama, United States
    • Mobile, Alabama, United States
    • Muscle Shoals, Alabama, United States
    • Pell City, Alabama, United States
  • Arizona
    • Goodyear, Arizona, United States
    • Phoenix, Arizona, United States
    • Tempe, Arizona, United States
    • Tucson, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Anaheim, California, United States
    • El Cajon, California, United States
    • Fresno, California, United States
    • Fullerton, California, United States
    • La Mesa, California, United States
    • Laguna Hills, California, United States
    • Los Angeles, California, United States
    • Mission Hills, California, United States
    • National City, California, United States
    • Newport Beach, California, United States
    • Orange, California, United States
    • Paramount, California, United States
    • Pismo Beach, California, United States
    • Redondo Beach, California, United States
    • San Diego, California, United States
    • San Francisco, California, United States
    • San Franciso, California, United States
    • Stockton, California, United States
    • Thousand Oaks, California, United States
    • Torrance, California, United States
    • Valley Village, California, United States
    • Westlake Village, California, United States
  • Colorado
    • Denver, Colorado, United States
    • Lakewood, Colorado, United States
  • Connecticut
    • Bridgeport, Connecticut, United States
    • Danbury, Connecticut, United States
  • Delaware
    • Seaford, Delaware, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Boynton Beach, Florida, United States
    • Brandon, Florida, United States
    • Chipley, Florida, United States
    • Clearwater, Florida, United States
    • Cocoa, Florida, United States
    • Coral Gables, Florida, United States
    • Coral Springs, Florida, United States
    • Crystal River, Florida, United States
    • Delray Beach, Florida, United States
    • Hialeah, Florida, United States
    • Hollywood, Florida, United States
    • Inverness, Florida, United States
    • Jacksonville, Florida, United States
    • Jacksonville Beach, Florida, United States
    • Melbourne, Florida, United States
    • Miami, Florida, United States
    • North Miami Beach, Florida, United States
    • Ocala, Florida, United States
    • Oviedo, Florida, United States
    • Pembroke Pines, Florida, United States
    • Sarasota, Florida, United States
    • St. Petersburg, Florida, United States
    • Tampa, Florida, United States
    • Trinity, Florida, United States
    • Vero Bearch, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Augusta, Georgia, United States
    • Calhoun, Georgia, United States
    • Conyers, Georgia, United States
    • Cumming, Georgia, United States
    • Norcross, Georgia, United States
    • Roswell, Georgia, United States
    • Suwanee, Georgia, United States
    • Woodstock, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
    • LaGrange, Illinois, United States
    • Springfield, Illinois, United States
  • Indiana
    • Anderson, Indiana, United States
    • Avon, Indiana, United States
    • Elkhart, Indiana, United States
    • Greenfield, Indiana, United States
    • Indianapolis, Indiana, United States
    • Muncie, Indiana, United States
  • Iowa
    • Ames, Iowa, United States
    • Council Bluffs, Iowa, United States
    • Waterloo, Iowa, United States
  • Kansas
    • Augusta, Kansas, United States
    • Hutchinson, Kansas, United States
    • Newton, Kansas, United States
    • Topeka, Kansas, United States
    • Wichita, Kansas, United States
  • Kentucky
    • Elizabethtown, Kentucky, United States
  • Louisiana
    • Marrero, Louisiana, United States
    • Monroe, Louisiana, United States
    • Natchitoches, Louisiana, United States
    • New Orleans, Louisiana, United States
    • Sherveport, Louisiana, United States
  • Maine
    • Portland, Maine, United States
  • Maryland
    • Annapolis, Maryland, United States
    • Balitmore, Maryland, United States
    • Baltimore, Maryland, United States
  • Massachusetts
    • Fall River, Massachusetts, United States
    • Hyannis, Massachusetts, United States
    • Natick, Massachusetts, United States
    • Springfield, Massachusetts, United States
  • Michigan
    • Bay City, Michigan, United States
    • Cadillac, Michigan, United States
    • Flint, Michigan, United States
    • Kalamazoo, Michigan, United States
    • Mt. Clemens, Michigan, United States
    • Novi, Michigan, United States
    • Pontiac, Michigan, United States
    • Saginaw, Michigan, United States
    • Troy, Michigan, United States
  • Minnesota
    • Baxter, Minnesota, United States
    • St. Cloud, Minnesota, United States
    • St. Paul, Minnesota, United States
  • Missouri
    • Columbia, Missouri, United States
    • Kansas City, Missouri, United States
    • St. Louis, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Hampshire
    • Nashua, New Hampshire, United States
  • New Jersey
    • Bridgewater, New Jersey, United States
    • Elizabeth, New Jersey, United States
    • Haddon Heights, New Jersey, United States
    • Linden, New Jersey, United States
    • Mine Hill, New Jersey, United States
    • Somerset, New Jersey, United States
    • South Plainfield, New Jersey, United States
    • Toms Rivers, New Jersey, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • New York
    • Brooklyn, New York, United States
    • Buffalo, New York, United States
    • Mineola, New York, United States
    • New York, New York, United States
    • Saratoga Springs, New York, United States
    • Smithtown, New York, United States
    • Syracuse, New York, United States
  • North Carolina
    • Burlington, North Carolina, United States
    • Calabash, North Carolina, United States
    • Charlotte, North Carolina, United States
    • Durham, North Carolina, United States
    • Greensboro, North Carolina, United States
    • Hickory, North Carolina, United States
    • Lenoir, North Carolina, United States
    • Mooresville, North Carolina, United States
    • Morganton, North Carolina, United States
    • Raleigh, North Carolina, United States
    • Rocky Mount, North Carolina, United States
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Akron, Ohio, United States
    • Canton, Ohio, United States
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
    • Columbus, Ohio, United States
    • Fairview Park, Ohio, United States
    • Gallipolis, Ohio, United States
    • Kettering, Ohio, United States
    • Marion, Ohio, United States
    • Middleburg Heights, Ohio, United States
    • Perrysburg, Ohio, United States
    • Springfield, Ohio, United States
    • Toledo, Ohio, United States
    • Willoughby Hills, Ohio, United States
  • Oklahoma
    • Norman, Oklahoma, United States
    • Oklahoma City, Oklahoma, United States
    • Tulsa, Oklahoma, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Chambersburg, Pennsylvania, United States
    • Hanleysville, Pennsylvania, United States
    • Harleysville, Pennsylvania, United States
    • Levittown, Pennsylvania, United States
    • Norristown, Pennsylvania, United States
    • Philadelphi, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
    • Scotland, Pennsylvania, United States
    • Uniontown, Pennsylvania, United States
  • Rhode Island
    • East Providence, Rhode Island, United States
    • Pawtucket, Rhode Island, United States
  • South Carolina
    • Columbia, South Carolina, United States
    • Greer, South Carolina, United States
    • Laurens, South Carolina, United States
    • Simpsonville, South Carolina, United States
  • Tennessee
    • Bristol, Tennessee, United States
    • Crossville, Tennessee, United States
    • Jackson, Tennessee, United States
    • Kingsport, Tennessee, United States
    • Nashville, Tennessee, United States
    • Oak Ridge, Tennessee, United States
    • Tullahoma, Tennessee, United States
  • Texas
    • Austin, Texas, United States
    • Carrollton, Texas, United States
    • Dallas, Texas, United States
    • Fort Worth, Texas, United States
    • Houston, Texas, United States
    • Irving, Texas, United States
    • Katy, Texas, United States
    • Midland, Texas, United States
    • Odessa, Texas, United States
    • Pearland, Texas, United States
    • San Antonio, Texas, United States
    • Spring, Texas, United States
    • Tomball, Texas, United States
    • Victoria, Texas, United States
  • Utah
    • Bountiful, Utah, United States
    • Layton, Utah, United States
    • Salt Lake City, Utah, United States
  • Virginia
    • Alexandria, Virginia, United States
    • Danville, Virginia, United States
    • Falls Church, Virginia, United States
    • Hampton, Virginia, United States
    • Manassas, Virginia, United States
  • Washington
    • Wenatchee, Washington, United States
  • West Virginia
    • Huntington, West Virginia, United States
    • Lewisburg, West Virginia, United States
  • Wisconsin
    • La Crosse, Wisconsin, United States
    • Madison, Wisconsin, United States
    • Milwaukee, Wisconsin, United States
    • Wauwatosa, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements, including scheduled clinic appointments.
2. 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.
3. Has a diagnosis of type 2 diabetes mellitus.
4. Has an glycosylated hemoglobin (HbA1c) level between 7.0% and 10.5%, inclusive, at Screening. HbA1c testing may be repeated once during Screening.

5. Meets at least one (1) of the following three (3) High Risk Categories (a-c ):

   1. A documented history of myocardial infarction (MI) occurring no less than 2 months (60 days) and no greater than 24 months prior to Screening.
   2. 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 ≤0.85. 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).

   3. 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):

   4. Stable angina with coronary disease documented by the presence of inducible ischemia or scar by stress myocardial perfusion imaging (MPI), echocardiogram or magnetic resonance imaging (MRI) in the past 24 months.
   5. Multi vessel coronary disease, based on coronary angiography, with or without angina, documented by >50% diameter stenosis in at least 2 of the 3 major coronary distributions.
   6. A history of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) at least 2 months prior to Screening.
   7. The subject has diabetic nephropathy plus (2) of the clinical criteria listed below (i. to vi.). Diabetic nephropathy is defined as either urinary albumin excretion ≥ 30 µg/mg creatinine (3.4 mg/mmol creatinine) (based on a random spot collection) or urinary albumin excretion ≥ 30 mg/24h (based on a 24 h or timed collection). Results must be confirmed on at least two specimens collected within 12 months prior to Screening and no more than 6 months apart: i)Duration of diabetes ≥ 10 years on pharmacological treatment documented within medical records. ii) Confirmed systolic blood pressure (SBP) ≥150 mm Hg on 2 separate days during Screening despite treatment with at least 2 anti-hypertensive medications administered at doses considered optimal by local standard of care. iii) Presence of dyslipidemia as defined by any one (1) of the following confirmed at screening: A. Low density lipoprotein (LDL) > 100 mg/dl (2.59 mmol/L) while on statin therapy administered at maximum tolerated dose or optimal dose based on local standard of care for at least 4 weeks prior to screening. B. LDL > 130 mg/dL (3.37 mmol/L) when not on statin therapy. C. High density lipoprotein (HDL) < 40 mg/dL (1.04 mmol/L) in males or < 45 mg/dL (1.17 mmol/L) in females. D. Fasting Triglyceride >200 mg/dL(2.26 mmol/L). iv) Currently smoking >10 cigarettes per day at Screening. v) Male ≥65 years of age or female ≥70 years of age. vi) Highly selective C-reactive protein (hs-CRP) > 2.0 mg/L in the absence of intercurrent infection or acute process.

   h.) The subject meets at least five (5) of the following clinical criteria: i.) Duration of diabetes ≥10 years on pharmacological treatment documented within medical records. ii) Confirmed systolic blood pressure (SBP) ≥150 mm Hg on 2 separate days during Screening despite treatment with at least 2 anti-hypertensive medications administered at doses considered optimal by local standard of care. iii) Presence of dyslipidemia as defined by any one (1) of the following confirmed at screening: A. Low density lipoprotein (LDL) > 100 mg/dl (2.59 mmol/L) while on statin therapy administered at maximum tolerated dose or optimal dose based on local standard of care for at least 4 weeks prior to screening. B. LDL > 130 mg/dL (3.37 mmol/L) when not on statin therapy. C. High density lipoprotein (HDL) < 40 mg/dL (1.04 mmol/L) in males or < 45 mg/dL (1.17 mmol/L) in females. D. Fasting Triglyceride >200 mg/dL(2.26 mmol/L). iv) Currently smoking >10 cigarettes per day at Screening. v) Male ≥65 years of age or female ≥70 years of age. vi) Highly selective C-reactive protein (hs-CRP) > 2.0 mg/L in the absence of intercurrent infection or acute process.

6. Is able and willing to monitor glucose with a home glucose monitor and consistently record his or her own blood glucose concentrations in patient diaries.
7. A female of childbearing potential who is sexually active with a non-sterilized male partner agrees to routinely use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose of study drug.
8. Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN) and if ALT or AST elevated above ULN, have chronic, well-compensated liver disease documented by usual clinical parameters.

Exclusion Criteria:

1. 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.
2. Has been randomized into a previous TAK-875 study.
3. 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. Is diagnosed with type 1 diabetes mellitus or latent autoimmune diabetes in adults.
5. Is hemodynamically unstable, including severe heart failure (New York Heart Association Class IV) at Screening.
6. 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).
7. Has ALT and/or AST levels >3.0x ULN at Screening.
8. 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.
9. 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.
10. Has uncontrolled thyroid disease, as determined by the investigator and/or clinical investigation.
11. Has a known history of infection with human immunodeficiency virus (HIV).
12. Has a known active infection with Hepatitis B virus (HBV), or Hepatitis C virus (HCV) requiring antiviral treatment.
13. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
14. Has any major illness or condition that, in the investigator's opinion, prohibits the patient from participating in the study or meeting the planned visit schedule.
15. Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to TAK-875.
16. If female, 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. 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. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-875 50 mg; TAK-875 50 mg tablets, orally, once daily for up to 6 years.	Drug: TAK-875; TAK-875 tablets
Placebo Comparator: Placebo; TAK-875 placebo-matching tablets, orally, once daily for up to 6 years.	Drug: TAK-875 Placebo; TAK-875 placebo-matching tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Occurrence of Any Component of Primary Major Adverse Cardiovascular Event (MACE) Composite	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).	Baseline up to end of study (up to Day 588)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Occurrence of Any Component of Secondary Major Adverse Cardiovascular Event (MACE) Composite	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.	Baseline up to end of study (up to Day 588)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Sr. Medical Director Clinical Science, Takeda

Publications and helpful links

General Publications

• Shavadia JS, Sharma A, Gu X, Neaton J, DeLeve L, Holmes D, Home P, Eckel RH, Watkins PB, Granger CB. Determination of fasiglifam-induced liver toxicity: Insights from the data monitoring committee of the fasiglifam clinical trials program. Clin Trials. 2019 Jun;16(3):253-262. doi: 10.1177/1740774519836766. Epub 2019 Mar 18.
• Menon V, Lincoff AM, Nicholls SJ, Jasper S, Wolski K, McGuire DK, Mehta CR, Rosenstock J, Lopez C, Marcinak J, Cao C, Nissen SE; GRAND 306 Investigators. Fasiglifam-Induced Liver Injury in Patients With Type 2 Diabetes: Results of a Randomized Controlled Cardiovascular Outcomes Safety Trial. Diabetes Care. 2018 Dec;41(12):2603-2609. doi: 10.2337/dc18-0755.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: May 29, 2012
• First Submitted That Met QC Criteria: May 31, 2012
• First Posted (Estimate): June 1, 2012

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: TAK-875_306; 2011-001732-37 (EudraCT Number); U1111-1129-7824 (Registry Identifier: WHO); TAK-875_306CTIL (Registry Identifier: Israel MOH); DOH-27-0313-4117 (Registry Identifier: SANCTR); 12/SC/0504 (Registry Identifier: NRES); NMRR-12-433-12087 (Registry Identifier: NMRR (Malaysia)); PHRR130916-000119 (Registry Identifier: PHRR (Philippines)); 1015031332 (Registry Identifier: TCTIN)