Comparison of TAK-875 to Placebo as an Add-on to Glimepiride 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:
NCT01829477
First received: April 9, 2013
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the effect of TAK-875 compared to placebo on glycemic control over a 24-week Treatment Period when used as an add-on to glimepiride in addition to diet and exercise.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: TAK-875
Drug: TAK-875 Placebo
Drug: Glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: 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, Placebo-Controlled, 24-Week Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 50 mg Compared With Placebo as an Add-on to Glimepiride 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: 33
Study Start Date: July 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAK-875 50 mg
TAK-875 50 mg tablet, orally, once daily and glimepiride 6 mg (or Maximum Tolerated Dose), tablets, orally, once daily for up to 24 weeks.
Drug: TAK-875
TAK-875 50 mg tablets
Drug: Glimepiride
Glimepiride tablet.
Other Name: Amaryl
Placebo Comparator: Placebo
TAK-875 placebo-matching tablet, orally, once daily and glimepiride 6 mg (or Maximum Tolerated Dose), tablets, orally, once daily for up to 24 weeks.
Drug: TAK-875 Placebo
TAK-875 placebo-matching tablets
Drug: Glimepiride
Glimepiride tablet.
Other Name: Amaryl

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 glycosylated hemoglobin (blood glucose combined with hemoglobin, also known as HbA1c) and blood sugar levels in people who take TAK-875 in addition to glimepiride and diet and exercise.

The study will enroll approximately 260 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. This multi-center trial will be conducted in North America and Europe. The overall time to participate in this study is up to 44 weeks and participants will make up to 17 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, the participant 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. Male or female and aged 18 or older with a historical diagnosis of type 2 diabetes mellitus (T2DM).
  4. Has a glycosylated hemoglobin (HbA1c) of 7.0% to10.0%, inclusive at screening, and has been treated with diet and exercise and a sulfonylurea for at least 12 weeks.
  5. Has a body mass index (BMI) ≤45 kg/m2 at Screening.
  6. 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 (PRN) use of prescription or over-the-counter medication 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 re-screened after the new regimen has been stabilized.
  7. A female of childbearing potential who is sexually active with a non-sterilized male partner agrees to use routinely 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. Is able and willing to monitor glucose with a sponsor-provided home glucose monitor and consistently record his or her own blood glucose concentrations and participant diaries.

Exclusion Criteria:

  1. Has received any investigational compound within 30 days prior to Screening or has received an investigational antidiabetic drug within 3 months prior to Screening.
  2. Has participated in 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, child, 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 gm/L) for males and ≤10 g/dL (≤100 gm/L) for females at Screening.
  6. Has a systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥95 mm Hg at Screening (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 based on the second measurement).
  7. 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.
  8. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2.0x the upper limit of normal (ULN) at Screening.
  9. 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.
  10. Has a serum creatinine ≥1.5 mg/dL (≥133 μmol/L) [if male] or ≥1.4 mg/dL (≥124 μmol/L) [if female] and/or estimated (based on Modification of Diet in Renal Disease [MDRD] calculation) glomerular filtration rate (GFR) <60 mL/min/1.73m2 (regardless of gender) at Screening.
  11. Has uncontrolled thyroid disease.
  12. Has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
  13. Has had gastric banding or gastric bypass surgery within 1 year prior to Screening.
  14. Has known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency, which increases risk for hemolytic anemia by sulfonylurea treatment.
  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, unstable angina pectoris, clinically significant abnormal electrocardiogram (ECG), cerebrovascular accident or transient ischemic attack within 3 months prior or at Screening.
  17. Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of TAK-875 or glimepiride.
  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. Received excluded medications prior to Screening or is expected to receive excluded medication.
  20. If female, the participant is pregnant (confirmed by laboratory testing, ie, serum 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: NCT01829477

  Show 69 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01829477     History of Changes
Other Study ID Numbers: TAK-875_309, 2013-000007-17, U1111-1138-8680
Study First Received: April 9, 2013
Last Updated: January 23, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal
Hungary: National Institute of Pharmacy
Romania: National Medicines Agency
Canada: Health Canada
Slovakia: State Institute for 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
Glimepiride
Anti-Arrhythmia Agents
Cardiovascular Agents
Hypoglycemic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014