Clinical trial NCT01456195: Comparison of TAK-875 (Fasiglifam) With Placebo in Participants With Type 2 Diabetes
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 25 mg and 50 mg Compared With Placebo in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-10-20
Enrollment: 421
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 determine the efficacy and safety of TAK-875 (fasiglifam), once daily (QD), in participants with type 2 diabetes mellitus (T2DM).

Detailed description: TAK-875 is being developed at Takeda Development Center, Inc. as an adjunct to diet and exercise to improve glycemic control in patients with T2DM.

This study will investigate TAK-875 in participants with type 2 diabetes mellitus who have been treated with only diet and exercise for at least 12 weeks prior to Screening, who have taken ≤7 days of any antidiabetic agent within the 12 weeks prior to Screening, and whose glycemic control is inadequate.

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. The participant is male or female and 18 years of age or older with a historical diagnosis of T2DM.
4. The participant has been treated with only diet and exercise for at least 12 weeks prior to Screening and has an HbA1c concentration between 7.0 % and 10.5%, inclusive, at Screening.
5. The participant has received ≤7 days of any antidiabetic agent within 12 weeks prior to Screening.
6. The participant 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 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.
8. The participant is able and willing to monitor glucose with a home glucose monitor and consistently record his or her own blood glucose concentrations and complete participant diaries.
9. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely 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.

Additional Inclusion Criteria prior to Randomization

1. The participant has an HbA1c concentration between 7.0 and 10.5%, inclusive, and a fasting plasma glucose (FPG) ≤270 mg/dL (≤15.0 mmol/L) at Week -1 Visit. (If the participant does not qualify for randomization based on these criteria, the assessments may be repeated weekly, for a maximum of 2 additional weeks).
2. The participant's overall compliance with single-blind study medication during the Placebo Run-in Period is at least 75% and does not exceed 125% based on tablet counts performed by the study staff.
3. A female participant of childbearing potential must have a negative urine hCG pregnancy test at Baseline (Visit 4) prior to Randomization and prior to administration of the first dose of double-blind study medication

Exclusion Criteria:

1. The participant 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 participant has been randomized in a previous TAK-875 study.
3. The participant 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 (e.g., spouse, parent, child, or sibling; biological or legally adopted) or may consent under duress.
4. The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
5. The participant has a hemoglobin ≤12 g/dL (≤120 gm/L) for males and ≤10 g/dL (≤100 gm/L) for females at Screening.
6. The participant 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. The participant 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 participant has an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels \>2.0x the upper limit of normal (ULN) at Screening.
9. The participant 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. The participant has a serum creatinine ≥1.5 mg/dL(≥133 µmol/L) \[males\] and ≥1.4 mg/dL (≥124 µmol/L) \[females\] and/or estimated glomerular filtration rate (GFR) \<60 mL/min/1.73m\^2 at Screening.
11. The participant has uncontrolled thyroid disease.
12. The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
13. The participant has had gastric banding or gastric bypass surgery within one year prior to Screening.
14. The participant has a known history of infection with human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).
15. The participant 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.
16. The participant has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of TAK-875.
17. The participant has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
18. The participant received excluded medications prior to Screening or is expected to receive excluded medication.
19. If female, the participant is pregnant (confirmed by laboratory testing, i.e., 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.
20. The participant is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.
21. The participant 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.

Additional Exclusion Criteria prior to Randomization

1. The participant received excluded medications during the Placebo Run-in Period. (Topical and inhaled corticosteroids are allowed).
2. The participant has a systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥95 mm Hg at Baseline (Visit 4) (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).

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c)
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Incidence of HbA1c <7%
timeFrame: Week 24
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: Baseline and Week 24
measure: Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Meal Tolerance Test (MTT)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
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state: Alabama
city: Muscle Shoals
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city: Goodyear
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state: Arizona
city: Phoenix
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state: Arizona
city: Long Beach
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state: California
city: North Hollywood
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city: Palm Springs
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state: California
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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: Picayune
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state: Mississippi
city: Omaha
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state: Nebraska
city: Elizabeth
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state: New Jersey
city: Charlotte
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state: North Carolina
city: Greensboro
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state: North Carolina
city: Mooresville
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state: North Carolina
city: Morganton
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Maumee
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state: Ohio
city: Oklahoma City
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state: Oklahoma
city: Harleysville
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state: Pennsylvania
city: Levittown
country: United States
state: Pennsylvania
city: Uniontown
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state: Pennsylvania
city: Greer
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state: South Carolina
city: Crossville
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state: Tennessee
city: Carrollton
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state: Texas
city: Dallas
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state: Texas
city: El Pasco
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state: Texas
city: Fort Worth
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state: Texas
city: Ft. Worth
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state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: New Braunfels
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Spring
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state: Texas
city: Tomball
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Burke
country: United States
state: Virginia
city: Manassas
country: United States
state: Virginia
city: Ciudad Autonoma de Buenos Aires
country: Argentina
state: Ciudad Autonoma Buenos Aires
city: Villa Cabrera
country: Argentina
state: Cordoba
city: Ciudad Autonoma Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Corrientes
country: Argentina
city: Mendoza
country: Argentina
city: Byala
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Guatemala City
country: Guatemala
city: Guatemala
country: Guatemala
city: Quetzaltenango
country: Guatemala
city: Zacapa
country: Guatemala
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Kecskemet
country: Hungary
city: Komarom
country: Hungary
city: Szikszo
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Mexico
country: Mexico
state: Distrito Federal
city: Monterrey
country: Mexico
state: Nuevo León
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Dolny Kubin
country: Slovakia
city: Komarno
country: Slovakia
city: Levice
country: Slovakia
city: Pezinok
country: Slovakia
city: Prievidza
country: Slovakia
city: Trebisov
country: Slovakia
city: Trencin
country: Slovakia
city: Zilina
country: Slovakia
city: Dnipropetrovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Odesa
country: Ukraine
city: Simferopol
country: Ukraine
city: Ternopil
country: Ukraine
city: Vinnytsia
country: Ukraine
city: Zaporizhzhia
country: Ukraine
Study officials:
affiliation: Takeda
name: Senior 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.