Clinical trial NCT01829477: Comparison of TAK-875 to Placebo as an Add-on to Glimepiride in Patients With Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2013-04-11
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Percentage of Participants With HbA1c <7 % at Week 24.
timeFrame: Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
state: Alabama
city: Phoenix
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state: Arizona
city: Fresno
country: United States
state: California
city: Long Beach
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state: California
city: National City
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state: California
city: North Hollywood
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state: California
city: Pismo Beach
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state: California
city: Lakewood
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state: Colorado
city: Boynton Beach
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state: Florida
city: Bradenton
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state: Florida
city: Coral Gables
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state: Florida
city: Miami
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state: Florida
city: North Miami Beach
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state: Florida
city: Orlando
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state: Florida
city: Pembroke Pines
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state: Florida
city: Tampa
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state: Florida
city: Augusta
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state: Georgia
city: Conyers
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state: Georgia
city: Chicago
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state: Illinois
city: Lexington
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state: Kentucky
city: Oxon Hill
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state: Maryland
city: Flint
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state: Michigan
city: Omaha
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Nashua
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state: New Hampshire
city: Haddon Heights
country: United States
state: New Jersey
city: Rosedale
country: United States
state: New York
city: Morehead City
country: United States
state: North Carolina
city: Morganton
country: United States
state: North Carolina
city: Maumee
country: United States
state: Ohio
city: Hanleysville
country: United States
state: Pennsylvania
city: Uniontown
country: United States
state: Pennsylvania
city: Laurens
country: United States
state: South Carolina
city: Houston
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state: Texas
city: San Antonio
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state: Texas
city: Spring
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state: Texas
city: Tomball
country: United States
state: Texas
city: Manassas
country: United States
state: Virginia
city: Gabrovo
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Oakville
country: Canada
state: Ontario
city: Thornhill
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Budapest
country: Hungary
city: Godollo
country: Hungary
city: Kistelek
country: Hungary
city: Komarom
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Grodzisk Mazowiecki
country: Poland
city: Kamieniec Zabkowicki
country: Poland
city: Lodz
country: Poland
city: Oswiecim
country: Poland
city: Poznan
country: Poland
city: Pulawy
country: Poland
city: Rzeszow
country: Poland
city: Zgierz
country: Poland
city: Baia Mare
country: Romania
city: Ploiesti
country: Romania
city: Timisoara
country: Romania
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Dolny Kubin
country: Slovakia
city: Levice
country: Slovakia
city: Lucenec
country: Slovakia
city: Pezinok
country: Slovakia
city: Svidnik
country: Slovakia
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.