Comparison of TAK-875 to Placebo as an Add-on to Glimepiride in Subjects With Type 2 Diabetes

• Conditions: Type 2 diabetes mellitus (T2DM); MedDRA version: 14.1Level: LLTClassification code 10063624Term: Type II diabetes mellitus inadequate controlSystem Organ Class: 10027433 - Metabolism and nutrition disorders; MedDRA version: 14.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; MedDRA version: 14.1Level: LLTClassification code 10029505Term: Non-insulin-dependent diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; MedDRA version: 14.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; MedDRA version: 14.1Level: LLTClassification code 10012613Term: Diabetes mellitus non-insulin-dependentSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2013-000007-17-HU
• Lead Sponsor: Takeda Development Centre Europe Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-02
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

Main Criteria for Inclusion:
1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
2. The subject or, when applicable, the subject’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. The subject is male or female, aged at least 18 years or older with a historical diagnosis of T2DM.
4. The subject has an HbA1c of 7.0% to 10.0%, inclusive at Screening, and has been treated with diet and exercise and a sulfonylurea for at least 12 weeks.
5. The subject has a body mass index (BMI) =45 kg/m2 at screening.
6. Subjects regularly using other, nonexcluded 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.
7. A female subject of childbearing potential who is sexually active with a nonsterilized 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.
8. The subject 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 subject diaries.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

Main Criteria for Exclusion:
1. The subject 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. The subject has participated in a previous TAK-875 study.
3. The subject 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, sibling) or may consent under duress.
4. The subject donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
5. The subject has a hemoglobin =12 g/dL (=120 gm/L) for males and =10 g/dL (=100 gm/L) for females at Screening.
6. The subject has a systolic blood pressure =160 mm Hg or diastolic blood pressure =95 mm Hg at Screening (If the subject 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. The subject 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. The subject has an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2.0 x the upper limit of normal (ULN) at Screening.
9. The subject has a total bilirubin level greater than the ULN at Screening. Exception: if a subject has documented Gilbert’s Syndrome, the subject will be allowed with an elevated bilirubin level per the investigator’s discretion.
10. The subject 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. The subject has uncontrolled thyroid disease.
12. The subject has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
13. The subject has had gastric banding or gastric bypass surgery within 1 year prior to Screening.
14. The subject has known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency, which increases risk for hemolytic anemia by sulfonylurea treatment.
15. The subject has a known history of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
16. The subject 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. The subject has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of TAK-875 or glimepiride.
18. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
19. The subject received excluded medications prior to Screening or is expected to receive excluded medication listed in Section 7.4, Excluded Medications and Treatments.
20. If female, the subject 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 m

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of TAK-875 compared to placebo on glycemic control as assessed by glycosylated hemoglobin (HbA1c) change from Baseline over a 24-week Treatment Period when used as an add-on to glimepiride in addition to diet and exercise.;Secondary Objective: To evaluate the effect of TAK-875 compared to placebo as an add-on to glimepiride on other measures of glycemic control, including clinically meaningful levels of response in HbA1c, and fasting plasma glucose (FPG) change over a 24-week treatment period.;Primary end point(s): Change from Baseline in HbA1c to Week 24.;Timepoint(s) of evaluation of this end point: Timepoint for evaluation of primary endpoint will be week 24.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Incidence of HbA1c <7% at Week 24.<br>Change from Baseline in FPG to Week 24.;Timepoint(s) of evaluation of this end point: Timepoint for evaluation of secondary endpoint will be week 24.