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Comparison of TAK-875 With Sitagliptin When Used in Combination With Metformin in Patients 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:
NCT01834274
First received: April 12, 2013
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the efficacy of TAK-875 plus metformin compared with sitagliptin plus metformin on glycemic control over a 24-week Treatment Period.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: TAK-875
Drug: TAK-875 Placebo
Drug: Sitagliptin
Drug: Sitagliptin Placebo
Drug: Metformin
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 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

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:
  • Percentage of participants with HbA1c <7% at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of participants with glycosylated hemoglobin less than 7% after 24 weeks of treatment.

  • 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: 96
Study Start Date: June 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAK-875 50 mg
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: TAK-875
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: TAK-875 Placebo
TAK-875 placebo-matching tablets
Drug: Sitagliptin
Sitagliptin tablets
Drug: Metformin
Metformin tablets

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 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.

  Eligibility

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

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
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: NCT01834274

  Show 104 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01834274     History of Changes
Other Study ID Numbers: TAK-875_310, 2013-000542-19, U1111-1139-0467, DOH-27-0913-4426, NMRR-13-518-16346
Study First Received: April 12, 2013
Last Updated: January 23, 2014
Health Authority: United States: Food and Drug Administration
Argentina: National Administration of Drugs, Foods and Medical Devices (ANMAT)
Peru: General Directorate of Medicines, Supplies and Drugs (DIGEMID)
South Africa: Medicines Control Council
Canada: Health Canada
Croatia: Agency for Medicinal Products and Medical Devices
Hungary: Hungary: National Institute for Quality- and Organizational Development in Healthcare and Medicines
Russia: Federal Service on Surveillance in Healthcare
Ukraine: Ministry of Health
Malaysia: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal
Philippines: Bureau of Food and Drugs (BFAD)
Thailand: Bureau of Drug Control

Keywords provided by Takeda:
Drug Therapy

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

ClinicalTrials.gov processed this record on November 25, 2014