Clinical trial NCT01549964: Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes
Official title: A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-875 25 mg and 50 mg Compared to Placebo and Sitagliptin 100 mg When Used in Combination With Metformin in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Glycemic Control
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-03-09
Enrollment: 916
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 efficacy of 2 doses of TAK-875 (25 mg and 50 mg), once daily (QD), plus metformin compared to placebo plus metformin and sitagliptin plus metformin on lowering blood sugar.

Detailed description: TAK-875 is being developed at Takeda Development Center, Inc. as an adjunct to diet and exercise to improve glycemic control in participants with Type 2 Diabetes Mellitus (T2DM) whose blood glucose level is inadequately controlled with metformin.

This study will evaluate the efficacy of TAK-875 (25 mg and 50 mg) plus metformin compared to placebo plus metformin and sitagliptin plus metformin on glycemic control as measured by change from baseline in glycosylated hemoglobin (HbA1c) over a 24-week Treatment Period. Participants completing the 24-week Treatment Period may enter an optional 80-week extension period for a total of 104 weeks of treatment.

Due to concerns about potential 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. The participant is male or female and 18 years of age or older with a historical diagnosis of type II diabetes mellitus.
2. The participant meets one of the following criteria:

   1. The participant has an HbA1c level ≥7.5 and \<10.5%, and has been on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose \[MTD\]) of metformin for at least 2 months prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;
   2. The participant has an HbA1c level ≥7.5 and \<10.5%, and has been on a stable daily dose of \<1500 mg of metformin without documented MTD for at least 2 months prior to Screening. After completing the Screening Visit, this participant will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8-week Titration Period according to Study Schedule B. Following this 8-week period, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures including having an HbA1c level ≥7.5 and \<10.5%.
3. The participant has had no treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for ≤7 days within the 2 months prior to Screening).
4. The participant has a body mass index (BMI) ≤45 kg/m² at Screening.
5. Participants regularly using other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
6. 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 subject diaries.

Exclusion Criteria:

1. The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
2. Hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening Visit.
3. The participant has systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening Visit. (If the participant meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement.)
4. The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
5. The participant has had treatment for gastric banding or gastric bypass surgery within one year prior to Screening.
6. The participant had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c)
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Incidence of HbA1c <7%
timeFrame: 24 Weeks
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
state: Alabama
city: Mesa
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Chula Vista
country: United States
state: California
city: El Cajon
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Laguna Hills
country: United States
state: California
city: National City
country: United States
state: California
city: Paramount
country: United States
state: California
city: San Diego
country: United States
state: California
city: Stockton
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state: California
city: Tustin
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state: California
city: West Hills
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state: California
city: Trumbull
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state: Connecticut
city: Coral Gables
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state: Florida
city: Jacksonville
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state: Florida
city: Miami
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state: Florida
city: New Port Richey
country: United States
state: Florida
city: Ocala
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state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Meridian
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Greenfield
country: United States
state: Indiana
city: Muncie
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state: Indiana
city: Lexington
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state: Kentucky
city: Owensboro
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state: Kentucky
city: Hyattsville
country: United States
state: Maryland
city: Troy
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state: Michigan
city: Picayune
country: United States
state: Mississippi
city: St. Louis
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state: Missouri
city: Haddon Heights
country: United States
state: New Jersey
city: Rosedale
country: United States
state: New York
city: Calabash
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Monroe
country: United States
state: North Carolina
city: Morehead City
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Norman
country: United States
state: Oklahoma
city: Lancaster
country: United States
state: Pennsylvania
city: Levittown
country: United States
state: Pennsylvania
city: Spartanburg
country: United States
state: South Carolina
city: Crossville
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state: Tennessee
city: Memphis
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state: Tennessee
city: Carrollton
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state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: Katy
country: United States
state: Texas
city: McKinney
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Spring
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Camperdown
country: Australia
state: New South Wales
city: Maroubra
country: Australia
state: New South Wales
city: Redcliffe
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Daw Park
country: Australia
state: South Australia
city: Box Hill
country: Australia
state: Victoria
city: Fitzroy
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Byala
country: Bulgaria
city: Kazanlak
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Cakovec
country: Croatia
city: Karlovac
country: Croatia
city: Krapinske Toplice
country: Croatia
city: Rijeka
country: Croatia
city: Slavonski Brod
country: Croatia
city: Split
country: Croatia
city: Zadar
country: Croatia
city: Zagreb
country: Croatia
city: Beroun
country: Czech Republic
city: Brno
country: Czech Republic
city: Havlickuv Brod
country: Czech Republic
city: Kladno
country: Czech Republic
city: Kromeriz
country: Czech Republic
city: Mlada Boleslav
country: Czech Republic
city: Ostrava - Moravska Ostrava
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Pardubice
country: Czech Republic
city: Pisek
country: Czech Republic
city: Plzen
country: Czech Republic
city: Praha 11
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Praha 6
country: Czech Republic
city: Praha 8
country: Czech Republic
city: Usti nad Labem
country: Czech Republic
city: Baja
country: Hungary
city: Balatonfured
country: Hungary
city: Budaors
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Eger
country: Hungary
city: Godollo
country: Hungary
city: Gyongyos
country: Hungary
city: Gyula
country: Hungary
city: Hodmezovasarhely
country: Hungary
city: Kecskemet
country: Hungary
city: Kistelek
country: Hungary
city: Kisvarda
country: Hungary
city: Komarom
country: Hungary
city: Mohacs
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Pecs
country: Hungary
city: Szeged
country: Hungary
city: Szekszard
country: Hungary
city: Szikszo
country: Hungary
city: Szolnok
country: Hungary
city: Szombathely
country: Hungary
city: Urhida
country: Hungary
city: Veszprem
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Sesto San Giovanni
country: Italy
state: Milano
city: Firenze
country: Italy
city: Milano
country: Italy
city: Pavia
country: Italy
city: Goyang-si
country: Korea, Republic of
state: Gyeonggi-do
city: Seongnam-Si
country: Korea, Republic of
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Johor Bahru
country: Malaysia
state: Johor
city: Alor Setar
country: Malaysia
state: Kedah
city: Kota Bharu
country: Malaysia
state: Kelantan
city: Cheras
country: Malaysia
state: Kuala Lumpur
city: Lembah Pantai
country: Malaysia
state: Kuala Lumpur
city: Petaling Jaya
country: Malaysia
state: Selangor
city: Kelantan
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Banska Bystrica
country: Slovakia
city: Bardejov
country: Slovakia
city: Bratislava
country: Slovakia
city: Kosice - Saca
country: Slovakia
city: Kosice
country: Slovakia
city: Levice
country: Slovakia
city: Lucenec
country: Slovakia
city: Moldava nad Bodvou
country: Slovakia
city: Nitra
country: Slovakia
city: Pezinok
country: Slovakia
city: Presov
country: Slovakia
city: Prievidza
country: Slovakia
city: Sahy
country: Slovakia
city: Stropkov
country: Slovakia
city: Sturovo
country: Slovakia
city: Svidnik
country: Slovakia
city: Trebisov
country: Slovakia
city: Trencin
country: Slovakia
city: Zilina
country: Slovakia
city: Patumwan
country: Thailand
state: Bangkok
city: Rachathevi
country: Thailand
state: Bangkok
city: Rajtevi
country: Thailand
state: Bangkok
city: Ratchathewi
country: Thailand
state: Bangkok
city: Muang
country: Thailand
state: Chiang Mai
city: Muang
country: Thailand
state: Nakhon Ratchasima
city: Hatyai
country: Thailand
state: Songkhla
city: Bangkok
country: Thailand
city: Khon Kaen
country: Thailand
Study officials:
affiliation: Takeda
name: Senior Medical Director Clinical Science
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.