Efficacy and Safety of TAK-875 Compared to Glimepiride When Used With Metformin in Participants With Type 2 Diabetes

NCT01481116 | Terminated Phase 3 Results DMC

• 10 other identifiers: TAK-875_3042011-001731-24U1111-1124-2296TAK-875_304CTILDOH-27-0512-391311-057NMRR-11-882-10318HKCTR-161626212/WA/0245
• Study Type: interventional
• Target: 2,454
• Locations: 23 countries
• Sites: 226

Brief Summary

The purpose of this study is to determine the efficacy and safety of TAK-875, once daily (QD), plus metformin compared to glimepiride plus metformin in participants with type 2 diabetes mellitus (T2DM). The purpose of this study is to determine the efficacy and safety of TAK-875, once daily (QD), plus metformin compared to glimepiride plus metformin in participants with type 2 diabetes mellitus (T2DM).

Conditions

Diabetes Mellitus, Type 2

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in HbA1c at Weeks 78 and 104

  The change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) to be collected at Weeks 78 and 104 relative to baseline.

  Baseline and Weeks 78 and 104

Secondary Outcomes (6)

• Percentage of Participants With Hypoglycemia

  Day 1 up to Weeks 78 and 104

• Change From Baseline in Body Weight at Weeks 78 and 104

  Baseline and Weeks 78 and 104

• Change From Baseline in HbA1c at Weeks 26 and 52

  Baseline and Weeks 26 and 52

• Percentage of Participants With HbA1c <7%

  Weeks 26, 52, 78 and 104

• Percentage of Participants With HbA1c <7% for Participants Who Did Not Report Hypoglycemia

  Weeks 26, 52, 78 and 104

Study Arms (3)

TAK-875 25 mg QD

EXPERIMENTAL

Drug: TAK-875

TAK-875 50 mg QD

EXPERIMENTAL

Drug: TAK-875

Glimepiride 1-2 mg QD

ACTIVE COMPARATOR

Drug: Glimepiride

Interventions

TAK-875 DRUG

TAK-875 25 mg, tablets, orally, once daily and metformin ≥1500 mg or Maximum Tolerated Dose (MTD) for up to 104 weeks.

TAK-875 25 mg QD

Glimepiride DRUG

Glimepiride 1 mg, tablets, orally, once daily (up-titrated to 2 mg after 1 week of treatment. Up-titrated to a maximum of 6 mg in 2 mg increments/down titrated if recurrent (or severe) hypoglycemia occurs) and metformin ≥1500 mg or MTD for up to 104 weeks.

Glimepiride 1-2 mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant'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.
• The participant is male or female and 18 years of age or older with a historical diagnosis of T2DM.
• The participant meets one of the following criteria:
• The participant has an HbA1c level ≥7.0 and \<10.0%, and has been on a stable daily dose of ≥1500 mg (or documented MTD) of metformin for at least 2 months prior to Screening. This participant will immediately enter the Placebo Run-in Period, or;
• The participant has an HbA1c level ≥ 7.5 and \<10.5%, and has been on a stable daily dose of \<1500 mg of metformin without documented MTD for at least 2 months prior to Screening. After completing the Screening Visit, this participant will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8-week Titration Period. Following this 8-week period, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures and having an HbA1c concentration ≥7.0 and \<10.0%.
• The participant has had no treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for ≤7 days within the 2 months prior to Screening).
• The participant has a body mass index (BMI) of ≤45 kg/m2 at Screening.
• Participants regularly using other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
• The participant is able and willing to monitor glucose with a home glucose monitor and consistently record his or her own blood glucose concentrations and complete participant diaries.
• The participant has an HbA1c concentration ≥7.0% and \<10.0%, and a FPG ≤270 mg/dL (15.0 mmol/L) at the Week -1 Visit. (If the subject does not qualify for randomization based on these criteria, the assessment may be repeated weekly, for a maximum of 2 additional weeks).
• The participant's compliance with the single-blind study medication during the Placebo Run-in Period is at least 75% and does not exceed 125% based on tablet/capsule counts performed by the study staff.
• A female participant of childbearing potential must have a negative urine hCG pregnancy test at Baseline (Day 1) prior to Randomization and prior to administration of the first dose of double-blind study medication.

You may not qualify if:

• The participant has received any investigational compound within 30 days prior to Screening or has received an investigational antidiabetic drug within the 3 months prior to Screening.
• The participant has been randomized into a previous TAK-875 study
• The participant 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 (e.g., spouse, parent, child, sibling) or may consent under duress.
• The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
• The participant has a hemoglobin ≤12 g/dL (≤120 gm/L) for males and ≤10 g/dL (≤100 gm/L) for females at Screening.
• The participant has 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 participant has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels \>2.0x upper limit of normal (ULN) at Screening.
• The participant has a total bilirubin level greater than the ULN at Screening. Exception: if a participant has documented Gilbert's Syndrome the participant will be allowed with an elevated bilirubin level per the investigator's discretion.
• The participant has a serum creatinine ≥1.5 mg/dL(males) and ≥1.4 mg/dL(females) and/or estimated glomerular filtration rate (GFR) \<60 mL/min/1.73m2 at Screening.
• The participant has uncontrolled thyroid disease.
• The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
• The participant has had gastric banding, or gastric bypass surgery within one year prior to Screening.
• The participant has a known history of infection with human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).
• The participant had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal electrocardiogram (ECG), cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.
• The participant has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of TAK-875, metformin, or glimepiride.

Sponsors & Collaborators

• Takeda: lead

Study Sites (226)

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Dothan, Alabama, United States

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Muscle Shoals, Alabama, United States

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Goodyear, Arizona, United States

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Phoenix, Arizona, United States

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Tempe, Arizona, United States

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Long Beach, California, United States

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Mission Hills, California, United States

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North Hollywood, California, United States

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Norwalk, California, United States

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Pismo Beach, California, United States

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Bradenton, Florida, United States

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Clearwater, Florida, United States

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Coral Gables, Florida, United States

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Hialeah, Florida, United States

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Orlando, Florida, United States

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Pembroke Pines, Florida, United States

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Decatur, Georgia, United States

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Avon, Indiana, United States

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Topeka, Kansas, United States

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Oxon Hill, Maryland, United States

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Flint, Michigan, United States

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Jackson, Mississippi, United States

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Omaha, Nebraska, United States

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Elizabeth, New Jersey, United States

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Calabash, North Carolina, United States

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Charlotte, North Carolina, United States

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Greensboro, North Carolina, United States

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Mooresville, North Carolina, United States

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Morganton, North Carolina, United States

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Raleigh, North Carolina, United States

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Maumee, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Greer, South Carolina, United States

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Spartanburg, South Carolina, United States

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Dallas, Texas, United States

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El Paso, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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New Braunfels, Texas, United States

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San Antonio, Texas, United States

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Spring, Texas, United States

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Tomball, Texas, United States

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Salt Lake City, Utah, United States

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Burke, Virginia, United States

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Hampton, Virginia, United States

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Manassas, Virginia, United States

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Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

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Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

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Corrientes, Corrientes Province, Argentina

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Córdoba, Córdoba Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Córdoba, Argentina

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Canberra, Australian Capital Territory, Australia

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Brookvale, New South Wales, Australia

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Mosman, New South Wales, Australia

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Woy Woy, New South Wales, Australia

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Canberra, Australia

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Blagoevgrad, Bulgaria

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Gabrovo, Bulgaria

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Sevlievo, Bulgaria

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Sofia, Bulgaria

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Stara Zagora, Bulgaria

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Varna, Bulgaria

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Victoria, British Columbia, Canada

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Oakville, Ontario, Canada

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Ottawa, Ontario, Canada

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Thornhill, Ontario, Canada

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Toronto, Ontario, Canada

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Laval, Quebec, Canada

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Longueuil, Quebec, Canada

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Mirabel, Quebec, Canada

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Pointe-Claire, Quebec, Canada

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Saint-Laurent, Quebec, Canada

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Bogotá, Colombia

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Medellín, Colombia

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Benátky nad Jizerou, Czechia

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Brno, Czechia

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Choceň, Czechia

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České Budějovice, Czechia

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Jindřichův Hradec, Czechia

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Mariánské Lázně, Czechia

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Olomouc, Czechia

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Ostrava, Czechia

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Ostrava - Moravska Ostrava, Czechia

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Ostrava - Vitkovice, Czechia

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Prague, Czechia

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Praha 4 - Krc, Czechia

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Znojmo, Czechia

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Paide, Estonia

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Rakvere, Estonia

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Saku, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Võru, Estonia

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Hong Kong, Hong Kong

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New Territories, Hong Kong

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Ashkelon, Israel

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Beer Yaakov, Israel

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Beersheba, Israel

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Giv‘atayim, Israel

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Hadera, Israel

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Haifa, Israel

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Holon, Israel

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Jerusalem, Israel

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Kfar Saba, Israel

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Nahariya, Israel

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Petah Tikva, Israel

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Raanana, Israel

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Ramat Gan, Israel

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Rehovot, Israel

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Rishon LeZiyyon, Israel

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Safed, Israel

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Tel Aviv, Israel

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Jelgava, Latvia

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Limbaži, Latvia

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Ogre, Latvia

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Riga, Latvia

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Talsi, Latvia

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Valmiera, Latvia

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Alytus, Lithuania

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Vilnius, Lithuania

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Kuala Lumpur, Kuala Lumpur, Malaysia

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Malacca, Melaka, Malaysia

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Ipoh, Perak, Malaysia

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Taiping, Perak, Malaysia

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Taiping, Perak, Perak, Malaysia

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Putrajaya, Putrajaya, Malaysia

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Petaling Jaya, Selangor, Malaysia

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Terengganu, Terengganu, Malaysia

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Terengganu, Malaysia

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Mexico City, Mexico City, Mexico

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Cuernavaca, Morelos, Mexico

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Auckland, New Zealand

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Christchurch, New Zealand

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Hamilton, New Zealand

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Palmerston North, New Zealand

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Rotorua, New Zealand

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Tauranga, New Zealand

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Wellington, New Zealand

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Cebu City, Philippines

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Davao City, Philippines

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Iloilo City, Philippines

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Lipa City, Philippines

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Quezon City, Philippines

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Tarlac City, Philippines

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Taytay, Philippines

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Bialystok, Poland

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Bydgoszcz, Poland

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Gdansk, Poland

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Grodzisk Mazowiecki, Poland

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Kamieniec Ząbkowicki, Poland

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Katowice, Poland

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Lodz, Poland

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Lublin, Poland

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Oświęcim, Poland

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Parczew, Poland

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Poznan, Poland

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Puławy, Poland

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Płock, Poland

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Ruda Śląska, Poland

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Rzeszów, Poland

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Sopot, Poland

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Torun, Poland

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Wroclaw, Poland

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Zgierz, Poland

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Łęczyca, Poland

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Bacau, Romania

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Baia Mare, Romania

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Bucharest, Romania

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Constanța, Romania

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Iași, Romania

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Oradea, Romania

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Ploieşti, Romania

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Târgu Mureş, Romania

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Timișoara, Romania

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Kazan', Russia

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Kemerovo, Russia

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Krasnoyarsk, Russia

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Moscow, Russia

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Novosibirsk, Russia

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Saint Petersburg, Russia

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Yaroslavl, Russia

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Port Elizabeth, Eastern Cape, South Africa

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Bloemfontein, Free State, South Africa

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Johannesburg, Gauteng, South Africa

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Kempton Park, Gauteng, South Africa

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Krugersdorp, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Durban, KwaZulu-Natal, South Africa

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Middelburg, Mpumalanga, South Africa

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Cape Town, Western Cape, South Africa

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Somerset West, Western Cape, South Africa

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Stellenbosch, Western Cape, South Africa

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Worcester, Western Cape, South Africa

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Chia-Yi City, Taiwan

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New Taipei City, Taiwan

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Taichung, Taiwan

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Tainan, Taiwan

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Taipei, Taiwan

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Dnipropetrovsk, Ukraine

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Kiev, Ukraine

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Kyiv, Ukraine

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Luhansk, Ukraine

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Lviv, Ukraine

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Mykolayiv, Ukraine

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Poltava, Ukraine

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Ternopil, Ukraine

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Vinnytsia, Ukraine

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Zaporizhzhia, Ukraine

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Cardiff, Cardiff, United Kingdom

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Cheadle, Cheshire, United Kingdom

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Plymouth, Devon, United Kingdom

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Hull, East Riding of Yorkshire, United Kingdom

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Bexhill-on-Sea, East Sussex, United Kingdom

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Watford, Hertfordshire, United Kingdom

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Thornton-Cleveleys, Lancashire, United Kingdom

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Liverpool, Merseyside, United Kingdom

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Northwood, Middlesex, United Kingdom

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Bath, Somerset, United Kingdom

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Swansea, South Glamorgan, United Kingdom

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Related Publications (1)

• 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.

  PMID: 30880443 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

TAK-875; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

clinicaltrialregistry@tpna.com

+1-877-825-3327

Study Officials

• Senior Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2011
• First Posted: November 29, 2011
• Study Start: January 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 1, 2016
• Results First Posted: June 1, 2016

Record last verified: 2016-04

Locations

MY (9); NZ (7); CZ (13); ES (6); LA (6); RU (7); UA (12); ZA (12); GB (11); AU (5); CA (10); HK (2); RO (9); IL (17); CO (2); TW (5); BU (8); LI (4); ME (2); PL (20); US (46); PH (7); AR (6)