Comparison of TAK-875 to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes

This study has been terminated.
(Due to potential concerns about liver safety (See Detailed Description))
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01549964
First received: March 6, 2012
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the efficacy of 2 doses of TAK-875 (25 mg and 50 mg), once daily (QD), plus metformin compared to placebo plus metformin and sitagliptin plus metformin on lowering blood sugar.


Condition Intervention Phase
Glycemic Control
Drug: TAK-875
Drug: Sitagliptin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-875 25 mg and 50 mg Compared to Placebo and Sitagliptin 100 mg When Used in Combination With Metformin in Subjects With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change from Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 or final visit relative to baseline.


Secondary Outcome Measures:
  • Incidence of HbA1c <7% [ Time Frame: 24 Weeks. ] [ Designated as safety issue: No ]
    Incidence of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected over 24 weeks.

  • Change from Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between FPG collected at week 24 or final visit relative to baseline.


Enrollment: 916
Study Start Date: May 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAK-875 25 mg QD

TAK-875 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Drug: TAK-875
TAK-875 tablets
Experimental: TAK-875 50 mg QD

TAK-875 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Drug: TAK-875
TAK-875 tablets
Active Comparator: Sitagliptin 100 mg QD

Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

TAK-875 placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Drug: Sitagliptin
Sitagliptin tablets
Other Name: Januvia
Placebo Comparator: Placebo QD

TAK-875 placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment.

Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Drug: Placebo
Placebo-matching tablets

Detailed Description:

TAK-875 is being developed at Takeda Global Research and Development, Inc. as an adjunct to diet and exercise to improve glycemic control in participants with Type 2 Diabetes Mellitus (T2DM) whose blood glucose level is inadequately controlled with metformin.

This study will evaluate the efficacy of TAK-875 (25 mg and 50 mg) plus metformin compared to placebo plus metformin and sitagliptin plus metformin on glycemic control as measured by change from baseline in glycosylated hemoglobin (HbA1c) over a 24-week Treatment Period. Participants completing the 24-week Treatment Period may enter an optional 80-week extension period for a total of 104 weeks of treatment.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The participant is male or female and 18 years of age or older with a historical diagnosis of type II diabetes mellitus.
  2. The participant meets one of the following criteria:

    1. The participant has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose [MTD]) of metformin for at least 2 months prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;
    2. 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 according to Study Schedule B. Following this 8-week period, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures including having an HbA1c level ≥7.5 and <10.5%.
  3. 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).
  4. The participant has a body mass index (BMI) ≤45 kg/m² at Screening.
  5. 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.
  6. 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 subject diaries.

Exclusion Criteria:

  1. The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
  2. Hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening Visit.
  3. The participant has systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening Visit. (If the participant meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement.)
  4. The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
  5. The participant has had treatment for gastric banding or gastric bypass surgery within one year prior to Screening.
  6. The participant had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01549964

  Hide Study Locations
Locations
United States, Alabama
Muscle Shoals, Alabama, United States
United States, Arizona
Mesa, Arizona, United States
Peoria, Arizona, United States
Phoenix, Arizona, United States
United States, California
Chula Vista, California, United States
El Cajon, California, United States
La Mesa, California, United States
Laguna Hills, California, United States
National City, California, United States
Paramount, California, United States
San Diego, California, United States
Stockton, California, United States
Tustin, California, United States
West Hills, California, United States
United States, Connecticut
Trumbull, Connecticut, United States
United States, Florida
Coral Gables, Florida, United States
Jacksonville, Florida, United States
Miami, Florida, United States
New Port Richey, Florida, United States
Ocala, Florida, United States
West Palm Beach, Florida, United States
United States, Idaho
Meridian, Idaho, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Greenfield, Indiana, United States
Muncie, Indiana, United States
United States, Kentucky
Lexington, Kentucky, United States
Owensboro, Kentucky, United States
United States, Maryland
Hyattsville, Maryland, United States
United States, Michigan
Troy, Michigan, United States
United States, Mississippi
Picayune, Mississippi, United States
United States, Missouri
St. Louis, Missouri, United States
United States, New Jersey
Haddon Heights, New Jersey, United States
United States, New York
Rosedale, New York, United States
United States, North Carolina
Calabash, North Carolina, United States
Charlotte, North Carolina, United States
Monroe, North Carolina, United States
Morehead City, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Ohio
Cincinnati, Ohio, United States
Cleveland, Ohio, United States
Dayton, Ohio, United States
United States, Oklahoma
Norman, Oklahoma, United States
United States, Pennsylvania
Lancaster, Pennsylvania, United States
Levittown, Pennsylvania, United States
United States, South Carolina
Spartanburg, South Carolina, United States
United States, Tennessee
Crossville, Tennessee, United States
Memphis, Tennessee, United States
United States, Texas
Carrollton, Texas, United States
Houston, Texas, United States
Irving, Texas, United States
Katy, Texas, United States
McKinney, Texas, United States
Plano, Texas, United States
San Antonio, Texas, United States
Spring, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
West Jordan, Utah, United States
United States, Virginia
Richmond, Virginia, United States
Australia, New South Wales
Camperdown, New South Wales, Australia
Maroubra, New South Wales, Australia
Australia, Queensland
Redcliffe, Queensland, Australia
Australia, South Australia
Adelaide, South Australia, Australia
Daw Park, South Australia, Australia
Australia, Victoria
Box Hill, Victoria, Australia
Fitzroy, Victoria, Australia
Melbourne, Victoria, Australia
Bulgaria
Byala, Bulgaria
Kazanlak, Bulgaria
Plovdiv, Bulgaria
Sofia, Bulgaria
Croatia
Cakovec, Croatia
Karlovac, Croatia
Krapinske Toplice, Croatia
Rijeka, Croatia
Slavonski Brod, Croatia
Split, Croatia
Zadar, Croatia
Zagreb, Croatia
Czech Republic
Beroun, Czech Republic
Brno, Czech Republic
Havlickuv Brod, Czech Republic
Kladno, Czech Republic
Kromeriz, Czech Republic
Mlada Boleslav, Czech Republic
Ostrava, Czech Republic
Ostrava - Moravska Ostrava, Czech Republic
Pardubice, Czech Republic
Pisek, Czech Republic
Plzen, Czech Republic
Praha 11, Czech Republic
Praha 2, Czech Republic
Praha 5, Czech Republic
Praha 6, Czech Republic
Praha 8, Czech Republic
Usti nad Labem, Czech Republic
Hungary
Baja, Hungary
Balatonfured, Hungary
Budaors, Hungary
Budapest, Hungary
Debrecen, Hungary
Eger, Hungary
Godollo, Hungary
Gyongyos, Hungary
Gyula, Hungary
Hodmezovasarhely, Hungary
Kecskemet, Hungary
Kistelek, Hungary
Kisvarda, Hungary
Komarom, Hungary
Mohacs, Hungary
Nyiregyhaza, Hungary
Pecs, Hungary
Szeged, Hungary
Szekszard, Hungary
Szikszo, Hungary
Szolnok, Hungary
Szombathely, Hungary
Urhida, Hungary
Veszprem, Hungary
Zalaegerszeg, Hungary
Italy
Sesto San Giovanni, Milano, Italy
Firenze, Italy
Milano, Italy
Pavia, Italy
Korea, Republic of
Goyang-si, Gyeonggi-do, Korea, Republic of
Seongnam-Si, Gyeonggi-do, Korea, Republic of
Incheon, Korea, Republic of
Seoul, Korea, Republic of
Malaysia
Johor Bahru, Johor, Malaysia
Alor Setar, Kedah, Malaysia
Kota Bharu, Kelantan, Malaysia
Cheras, Kuala Lumpur, Malaysia
Lembah Pantai, Kuala Lumpur, Malaysia
Petaling Jaya, Selangor, Malaysia
Kelantan, Malaysia
Kuala Lumpur, Malaysia
Slovakia
Banska Bystrica, Slovakia
Bardejov, Slovakia
Bratislava, Slovakia
Kosice, Slovakia
Kosice - Saca, Slovakia
Levice, Slovakia
Lucenec, Slovakia
Moldava nad Bodvou, Slovakia
Nitra, Slovakia
Pezinok, Slovakia
Presov, Slovakia
Prievidza, Slovakia
Sahy, Slovakia
Stropkov, Slovakia
Sturovo, Slovakia
Svidnik, Slovakia
Trebisov, Slovakia
Trencin, Slovakia
Zilina, Slovakia
Thailand
Patumwan, Bangkok, Thailand
Rachathevi, Bangkok, Thailand
Rajtevi, Bangkok, Thailand
Ratchathewi, Bangkok, Thailand
Muang, Chiang Mai, Thailand
Muang, Nakhon Ratchasima, Thailand
Hatyai, Songkhla, Thailand
Bangkok, Thailand
Khon Kaen, Thailand
Sponsors and Collaborators
Takeda
Investigators
Study Director: Senior Medical Director Clinical Science Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01549964     History of Changes
Other Study ID Numbers: TAK-875_302, 2011-001752-10, U1111-1124-2225, NMRR-12-446-11314
Study First Received: March 6, 2012
Last Updated: January 23, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
Croatia: Ministry of Health and Social Care
Hungary: National Institute of Pharmacy
Slovakia: State Institute for Drug Control
Australia: Department of Health and Ageing Therapeutic Goods Administration
Thailand: Food and Drug Administration

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014