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

NCT ID: NCT01829477

Last Updated: 2016-06-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2014-02-28

Brief Summary

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.

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

TAK-875

Intervention Type: DRUG

TAK-875 50 mg tablets

Glimepiride

Intervention Type: DRUG

Glimepiride tablet.

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.

Group Type: PLACEBO_COMPARATOR

TAK-875 Placebo

Intervention Type: DRUG

TAK-875 placebo-matching tablets

Glimepiride

Intervention Type: DRUG

Glimepiride tablet.

Interventions

TAK-875

TAK-875 50 mg tablets

Intervention Type: DRUG

TAK-875 Placebo

TAK-875 placebo-matching tablets

Intervention Type: DRUG

Glimepiride

Glimepiride tablet.

Intervention Type: DRUG

Other Intervention Names

Amaryl

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Muscle Shoals, Alabama, United States

Phoenix, Arizona, United States

Fresno, California, United States

Long Beach, California, United States

National City, California, United States

North Hollywood, California, United States

Pismo Beach, California, United States

Lakewood, Colorado, United States

Boynton Beach, Florida, United States

Bradenton, Florida, United States

Coral Gables, Florida, United States

Miami, Florida, United States

North Miami Beach, Florida, United States

Orlando, Florida, United States

Pembroke Pines, Florida, United States

Tampa, Florida, United States

Augusta, Georgia, United States

Conyers, Georgia, United States

Chicago, Illinois, United States

Lexington, Kentucky, United States

Oxon Hill, Maryland, United States

Flint, Michigan, United States

Omaha, Nebraska, United States

Las Vegas, Nevada, United States

Nashua, New Hampshire, United States

Haddon Heights, New Jersey, United States

Rosedale, New York, United States

Morehead City, North Carolina, United States

Morganton, North Carolina, United States

Maumee, Ohio, United States

Hanleysville, Pennsylvania, United States

Uniontown, Pennsylvania, United States

Laurens, South Carolina, United States

Houston, Texas, United States

San Antonio, Texas, United States

Spring, Texas, United States

Tomball, Texas, United States

Manassas, Virginia, United States

Gabrovo, , Bulgaria

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Oakville, Ontario, Canada

Thornhill, Ontario, Canada

Toronto, Ontario, Canada

Budapest, , Hungary

Gödöllő, , Hungary

Kistelek, , Hungary

Komárom, , Hungary

Zalaegerszeg, , Hungary

Bialystok, , Poland

Gdansk, , Poland

Grodzisk Mazowiecki, , Poland

Kamieniec Ząbkowicki, , Poland

Lodz, , Poland

Oświęcim, , Poland

Poznan, , Poland

Puławy, , Poland

Rzeszów, , Poland

Zgierz, , Poland

Baia Mare, , Romania

Ploieşti, , Romania

Timișoara, , Romania

Banská Bystrica, , Slovakia

Bratislava, , Slovakia

Dolný Kubín, , Slovakia

Levice, , Slovakia

Lučenec, , Slovakia

Pezinok, , Slovakia

Svidník, , Slovakia

Countries

United States; Bulgaria; Canada; Hungary; Poland; Romania; Slovakia

References

Shavadia JS, Sharma A, Gu X, Neaton J, DeLeve L, Holmes D, Home P, Eckel RH, Watkins PB, Granger CB. Determination of fasiglifam-induced liver toxicity: Insights from the data monitoring committee of the fasiglifam clinical trials program. Clin Trials. 2019 Jun;16(3):253-262. doi: 10.1177/1740774519836766. Epub 2019 Mar 18.

Reference Type: DERIVED

PMID: 30880443 (View on PubMed)

Other Identifiers

2013-000007-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1138-8680

Identifier Type: REGISTRY

Identifier Source: secondary_id

164539

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-875_309

Identifier Type: -

Identifier Source: org_study_id