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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01549964




Registration number
NCT01549964
Ethics application status
Date submitted
6/03/2012
Date registered
9/03/2012
Date last updated
2/06/2016

Titles & IDs
Public title
Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes
Scientific 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
Secondary ID [1] 0 0
2011-001752-10
Secondary ID [2] 0 0
TAK-875_302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glycemic Control 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fasiglifam (TAK-875)
Treatment: Drugs - Sitagliptin
Treatment: Drugs - Placebo

Experimental: Fasiglifam (TAK-875) 25 mg - Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin =1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Experimental: Fasiglifam (TAK-875) 50 mg - Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin =1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Active comparator: Sitagliptin 100 mg - Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. TAK-875 placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin =1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Placebo comparator: Placebo - Fasiglifam (TAK-875) placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin =1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.


Treatment: Drugs: Fasiglifam (TAK-875)
Fasiglifam (TAK-875) tablets

Treatment: Drugs: Sitagliptin
Sitagliptin tablets

Treatment: Drugs: Placebo
Placebo-matching tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [1] 0 0
Incidence of HbA1c <7%
Timepoint [1] 0 0
24 Weeks
Secondary outcome [2] 0 0
Change From Baseline in Fasting Plasma Glucose (FPG)
Timepoint [2] 0 0
Baseline and Week 24

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2014
Sample size
Target
Accrual to date
Final
916
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
- Camperdown
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- Maroubra
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- Redcliffe
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- Adelaide
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- Daw Park
Recruitment hospital [6] 0 0
- Box Hill
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- Fitzroy
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- Melbourne
Recruitment postcode(s) [1] 0 0
- Camperdown
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- Maroubra
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- Redcliffe
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- Adelaide
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- Daw Park
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- Box Hill
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- Fitzroy
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- Melbourne
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01549964
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Senior Medical Director Clinical Science
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01549964