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Comparison of Fasiglifam (TAK-875) With Sitagliptin When Used in Combination With Metformin in Patients With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT01834274
Recruitment Status : Terminated (Due to potential concerns about liver safety (See Detailed Description))
First Posted : April 17, 2013
Results First Posted : September 28, 2015
Last Update Posted : September 28, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to evaluate the efficacy of fasiglifam (TAK-875) plus metformin compared with sitagliptin plus metformin on glycemic control over a 24-week Treatment Period.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Fasiglifam (TAK-875) Drug: Fasiglifam (TAK-875) Placebo Drug: Sitagliptin Drug: Sitagliptin Placebo Drug: Metformin Phase 3

Detailed Description:

The drug being tested in this study is called TAK-875. TAK-875 is being tested to treat people who have type 2 diabetes. This study will look at glycemic control in people who take TAK-875 in addition to metformin.

The study will enroll approximately 620 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
  • Sitagliptin 100 mg

All participants will be asked to take one tablet at the same time each day throughout the study. All participants will be asked to self-monitor their blood glucose levels and document any increases in blood glucose or symptoms of hypoglycemia in a diary.

This multi-center trial will be conducted in the United States, Latin America, Europe and Asia. The overall time to participate in this study is up to 42 weeks and participants will make up to 15 visits to the clinic.

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, 24-Week Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 50 mg Compared With Sitagliptin 100 mg When Used in Combination With Metformin in Subjects With Type 2 Diabetes
Study Start Date : June 2013
Primary Completion Date : March 2014
Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Fasiglifam 50 mg
Fasiglifam (TAK-875) 50 mg tablets, orally, once daily, Sitagliptin placebo-matching tablets, orally, once daily, and metformin stable dose ≥1500 mg (or maximum-tolerated dose), tablets, orally, daily for up to 24 weeks.
Drug: Fasiglifam (TAK-875)
Fasiglifam (TAK-875) tablets
Drug: Sitagliptin Placebo
Sitagliptin placebo-matching tablets
Drug: Metformin
Metformin tablets
Active Comparator: Sitagliptin 100 mg
Sitagliptin 100 mg, tablets, once daily, TAK-875 placebo-matching tablets, orally, once daily, and metformin stable dose ≥1500 mg (or maximum-tolerated dose), tablets, orally, daily for up to 24 weeks.
Drug: Fasiglifam (TAK-875) Placebo
Fasiglifam (TAK-875) placebo-matching tablets
Drug: Sitagliptin
Sitagliptin tablets
Drug: Metformin
Metformin tablets

Outcome Measures

Primary Outcome Measures :
  1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline and Week 24 ]
    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. A negative change from Baseline indicated improvement.

Secondary Outcome Measures :
  1. Percentage of Participants With HbA1c <7% at Week 24 [ Time Frame: Week 24 ]
    The percentage of participants with glycosylated hemoglobin less than 7% after 24 weeks of treatment.

  2. Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline and Week 24 ]
    The change between FPG collected at week 24 or final visit relative to Baseline. A negative change from Baseline indicated improvement.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
  2. 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.
  3. Is male or female and 18 years of age or older with a historical diagnosis of type 2 diabetes mellitus (T2DM).
  4. Meets one of the following criteria:.

    1. Has an HbA1c ≥8% 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 8 weeks prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;
    2. Has an HbA1c ≥8% and <10.5%, and has been on a stable daily dose of <1500 mg of metformin without documented MTD for at least 8 weeks prior to Screening. After completing the Screening Visit, these participants will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8- to 12-week Titration/Stabilization Period according to Study Schedule B. Following stable administration of metformin ≥1500 mg (or MTD) for 8 weeks, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures and have an HbA1c ≥8% and <10.5%.
  5. Has had no treatment with anti-diabetic agents other than metformin within 8 weeks prior to Screening (Exception: if a participant has received other anti-diabetic therapy for ≤7 days within the 8 weeks prior to Screening).
  6. Has a body mass index (BMI) ≤45 kg/m^2 at Screening.
  7. Participants regularly using other, non-excluded medications must be on a stable dose and regimen for at least 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator. Note: Participants who require initiation of a chronically administered medication(s) due to a disease or condition diagnosed at Screening must be rescreened after the new regimen has been stabilized.
  8. A female participant of childbearing potential who is sexually active with a non-sterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 30 days after the last dose of study drug.
  9. Is able and willing to monitor glucose with a sponsor-provided home glucose monitor and consistently record his or her own blood glucose concentrations in diaries.

Exclusion Criteria:

  1. Has received any investigational compound within 30 days prior to Screening or has received an investigational anti-diabetic drug within the 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 dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, or sibling) or may consent under duress.
  4. Has donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
  5. Has a hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening.
  6. Has systolic blood pressure ≥160 mm Hg or diastolic blood 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 and decision will be made on the second measurement.)
  7. Has history of cancer that has been in remission for <5 years prior to Screening. A history of basal cell carcinoma or stage I squamous cell carcinoma of the skin is allowed.
  8. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2 x upper limit of normal (ULN) at Screening.
  9. Has a total bilirubin level >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.
  10. Has serum creatinine ≥1.5mg/dL (≥133μmol/L) if male or ≥1.4 mg/dL (≥124 μmol/L) if female and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2 at Screening.
  11. Has uncontrolled thyroid disease as determined by the investigator.
  12. Has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
  13. Has a history of pancreatitis.
  14. Has a history of gastric banding or gastric bypass surgery within one year prior to Screening.
  15. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
  16. Had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction (MI), unstable angina pectoris, clinically significant abnormal electrocardiogram (ECG), cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.
  17. Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of TAK-875, metformin, or sitagliptin.
  18. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
  19. Has received excluded medications prior to Screening or is expected to receive excluded medications.
  20. If female, is pregnant (confirmed by laboratory testing, ie, serum/urine human chorionic gonadotropin (hCG), in females of childbearing potential) or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
  21. Is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.
  22. Has any other physical or psychiatric disease or condition that in the judgment of the investigator may affect life expectancy or may make it difficult to successfully manage and follow the participant according to the protocol.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01834274

  Hide Study Locations
United States, Alabama
Huntsville, Alabama, United States
United States, Arizona
Chandler, Arizona, United States
Glendale, Arizona, United States
United States, Arkansas
Little Rock, Arkansas, United States
United States, California
Fresno, California, United States
Garden Grove, California, United States
Modesto, California, United States
San Diego, California, United States
Thousand Oaks, California, United States
United States, Colorado
Lakewood, Colorado, United States
United States, Florida
Hallandale Beach, Florida, United States
Hialeah, Florida, United States
Miami Lakes, Florida, United States
Miami, Florida, United States
North Miami Beach, Florida, United States
North Miami, Florida, United States
Pembroke Pines, Florida, United States
Sanford, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
Conyers, Georgia, United States
Evans, Georgia, United States
United States, Idaho
Boise, Idaho, United States
United States, Illinois
Chicago, Illinois, United States
Evanston, Illinois, United States
United States, Iowa
Council Bluffs, Iowa, United States
United States, Kansas
Augusta, Kansas, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, New York
New York, New York, United States
United States, North Carolina
Durham, North Carolina, United States
Greensboro, North Carolina, United States
Hickory, North Carolina, United States
United States, Ohio
Carlisle, Ohio, United States
United States, Oklahoma
Oklahoma City, Oklahoma, United States
United States, Oregon
Medford, Oregon, United States
United States, South Carolina
Fort Mill, South Carolina, United States
Laurens, South Carolina, United States
Spartanburg, South Carolina, United States
United States, Tennessee
Knoxville, Tennessee, United States
United States, Texas
Austin, Texas, United States
Odessa, Texas, United States
San Antonio, Texas, United States
Sugar Land, Texas, United States
Victoria, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
Coronel Suarez, Buenos Aires, Argentina
Rosario, Santa Fe, Argentina
Ciudad Autonoma Buenos Aires, Argentina
Canada, Alberta
Calgary, Alberta, Canada
Red Deer, Alberta, Canada
Canada, British Columbia
Vancouver, British Columbia, Canada
Victoria, British Columbia, Canada
Canada, Manitoba
Winnipeg, Manitoba, Canada
Canada, Ontario
Etobicoke, Ontario, Canada
London, Ontario, Canada
Toronto, Ontario, Canada
Karlovac, Croatia
Krapinske Toplice, Croatia
Slavonski Brod, Croatia
Virovitica, Croatia
Zagreb, Croatia
Budapest, Hungary
Godollo, Hungary
Kistarcsa, Hungary
Satoraljaujhely, Hungary
Szeged, Hungary
Seri Manjung, Perak, Malaysia
Taiping, Perak, Perak, Malaysia
Taiping, Perak, Malaysia
Putrajaya, Selangor, Malaysia
Kelantan, Malaysia
Kuala Lumpur, Malaysia
Ica, Peru
Lima, Peru
Cebu City, Philippines
Iloilo City, Philippines
Marikina City, Philippines
Pasig, Philippines
Quezon City, Philippines
West Fairview, Quezon City, Philippines
Gdansk, Poland
Lodz, Poland
Oswiecim, Poland
Rzeszow, Poland
Sobotka, Poland
Wroclaw, Poland
Zgierz, Poland
Russian Federation
Barnaul, Russian Federation
Kemerovo, Russian Federation
Novosibirsk, Russian Federation
St. Petersburg, Russian Federation
South Africa
Bloemfontein, Free State, South Africa
Pretoria, Gauteng, South Africa
Durban, KwaZulu-Natal, South Africa
Cape Town, Western Cape, South Africa
Bangkoknoi, Bangkok, Thailand
Rajathevee, Bangkok, Thailand
Muang, Khon Kaen, Thailand
Klongluang, Pathum Thani, Thailand
Hat Yai, Songkhla, Thailand
Ivano-Frankivsk, Ukraine
Kharkiv, Ukraine
Kyiv, Ukraine
Lviv, Ukraine
Vinnytsia, Ukraine
Sponsors and Collaborators
Study Director: Medical Director Takeda
More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01834274     History of Changes
Other Study ID Numbers: TAK-875_310
2013-000542-19 ( EudraCT Number )
U1111-1139-0467 ( Registry Identifier: WHO UTN )
DOH-27-0913-4426 ( Registry Identifier: SANCTR (South Africa) )
NMRR-13-518-16346 ( Registry Identifier: NMRR (Malaysia) )
PHRR140127-000165 ( Registry Identifier: PHRR (Philippines) )
First Posted: April 17, 2013    Key Record Dates
Results First Posted: September 28, 2015
Last Update Posted: September 28, 2015
Last Verified: August 2015

Keywords provided by Takeda:
Drug Therapy

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