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
  Purpose
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.

Condition Intervention Phase
Glycemic Control
Drug: Fasiglifam (TAK-875)
Drug: Sitagliptin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 916
Study Start Date: April 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Fasiglifam (TAK-875)
Fasiglifam (TAK-875) tablets
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.
Drug: Fasiglifam (TAK-875)
Fasiglifam (TAK-875) tablets
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.
Drug: Sitagliptin
Sitagliptin tablets
Other Name: Januvia
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.
Drug: Placebo
Placebo-matching tablets

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01549964

  Show 164 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Senior Medical Director Clinical Science Takeda
  More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01549964     History of Changes
Other Study ID Numbers: TAK-875_302  2011-001752-10  U1111-1124-2225  NMRR-12-446-11314 
Study First Received: March 6, 2012
Results First Received: March 25, 2015
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
Croatia: Ministry of Health and Social Care
Hungary: National Institute of Pharmacy
Slovakia: State Institute for Drug Control
Australia: Department of Health and Ageing Therapeutic Goods Administration
Thailand: Food and Drug Administration

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Metformin
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2016