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Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes

This study has been terminated.
(Due to concerns about potential liver safety (See Detailed Description))
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01549964
First received: March 6, 2012
Last updated: April 20, 2016
Last verified: April 2016

March 6, 2012
April 20, 2016
April 2012
March 2014   (final data collection date for primary outcome measure)
Change From Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to Baseline. A Mixed Model Repeated Measures (MMRM) model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 or final visit relative to baseline.
Complete list of historical versions of study NCT01549964 on ClinicalTrials.gov Archive Site
  • Incidence of HbA1c <7% [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Incidence (percentage) of participants with glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than 7% at Week 24.
  • Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The change between FPG collected at week 24 relative to Baseline. A MMRM model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.
  • Incidence of HbA1c <7% [ Time Frame: 24 Weeks. ] [ Designated as safety issue: No ]
    Incidence of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected over 24 weeks.
  • Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The change between FPG collected at week 24 or final visit relative to baseline.
Not Provided
Not Provided
 
Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes
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
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Glycemic Control
  • Drug: Fasiglifam (TAK-875)
    Fasiglifam (TAK-875) tablets
  • Drug: Sitagliptin
    Sitagliptin tablets
    Other Name: Januvia
  • Drug: Placebo
    Placebo-matching tablets
  • 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.
    Intervention: Drug: Fasiglifam (TAK-875)
  • 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.
    Intervention: Drug: Fasiglifam (TAK-875)
  • 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.
    Intervention: Drug: Sitagliptin
  • 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.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
916
March 2014
March 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Bulgaria,   Croatia,   Czech Republic,   Hungary,   Italy,   Korea, Republic of,   Malaysia,   Slovakia,   Thailand
 
NCT01549964
TAK-875_302, 2011-001752-10, U1111-1124-2225, NMRR-12-446-11314
Yes
Not Provided
Not Provided
Takeda
Takeda
Not Provided
Study Director: Senior Medical Director Clinical Science Takeda
Takeda
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP