Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 25 and 50mg in Asia Pacific Adults With Type 2 Diabetes (GRAND-307)

This study has been terminated.
(Due to potential concerns about liver safety (See Detailed Description))
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01647542
First received: July 19, 2012
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of TAK-875 in Asia Pacific adults with type 2 diabetes mellitus (T2DM).


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: TAK-875
Drug: TAK-875 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 Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 24-week Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 25 and 50mg Compared With Placebo in Asia Pacific 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 from Baseline to Week 24 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).


Secondary Outcome Measures:
  • Percentage of Participants with HbA1c less than 7.0% [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of Participants with HbA1C less than 7.0% (as a percent of the total number of Participants in the study).

  • Change from Baseline in fasting plasma glucose [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The change from Baseline to Week 24 in fasting plasma glucose (the amount of glucose in blood after fasting for at least 10 hours).

  • Change from Baseline in 2-hour postprandial glucose following oral glucose tolerance test [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    During the oral glucose tolerance test (OGTT), patients will be given a standardized glucose solution to drink within 5 minutes after fasting for at least 10 hours prior. 2 hours after consuming the solution (postprandial), blood samples will be taken for glucose measurements. OGTT will be performed at Baseline and again at Week 24.


Enrollment: 393
Study Start Date: October 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAK-875 25 mg
TAK-875 25 mg tablets, orally, once daily for up to 24 weeks.
Drug: TAK-875
TAK-875 tablets
Experimental: TAK-875 50 mg
TAK-875 50 mg tablets, orally, once daily for up to 24 weeks.
Drug: TAK-875
TAK-875 tablets
Placebo Comparator: Placebo
TAK-875 placebo-matching tablets, orally, once daily for up to 24 weeks.
Drug: TAK-875 Placebo
TAK-875 placebo-matching tablets

Detailed Description:

The drug being tested in this study is called TAK-875. TAK-875 is being tested to treat people who have diabetes.

The study will enroll approximately 750 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

  • TAK-875 25 mg once daily
  • TAK-875 50 mg once daily
  • Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

All participants will be asked to take one tablet at the same time each day throughout the study. All participants will be asked to record any time they have low blood sugar symptoms in a diary.

This multi-centre trial will be conducted the Asia Pacific region. The overall time to participate in this study is 30 weeks. Participants will make 13 visits to the clinic.

Due to potential concerns about 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements.
  2. The patient or, when applicable, the patient'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. Male or female, aged at least 18 years or over the legal age of consent in countries where that is greater than 18 years, with a historical diagnosis of T2DM.
  4. Has an HbA1c of 7.0% to 10.0%, inclusive at screening, and has been treated with diet and exercise for at least 3 months.
  5. Has a body mass index (BMI) of ≤45 kg/m^2 at screening.
  6. Patients regularly using, 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 medication is allowed at the discretion of the investigator.
  7. A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use 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.
  8. 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. Is unable to understand the official language (verbal or written) of the country for which a certified translation of the approved informed consent is available.
  2. 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 (eg, spouse, parent, child, or sibling; biological or legally adopted) or may consent under duress.
  3. Has hemoglobin a level ≤12 g/dL (≤120 g/L) (males) and ≤10 g/dL (≤100 g/L) (females) at the Screening Visit.
  4. Has a history of any hemoglobinopathy that may affect determination of HbA1c.
  5. Donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
  6. Has systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening or Baseline (If the patient meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after initial measurement and decision will be made based on the second measurement).
  7. Had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal electrocardiogram, cerebrovascular accident or transient ischemic attack within 3 months prior or at Screening.
  8. Has a serum creatinine level of ≥1.5 mg/dL (males) and ≥1.4 mg/dL (females) and/or estimated glomerular filtration rate (GFR) <60 mL/min/1.73m^2 at Screening.
  9. Has uncontrolled thyroid disease.
  10. Has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
  11. Has a history or treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery.
  12. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2.0x the upper limit of normal range (ULN) at Screening.
  13. Has a total bilirubin level greater than the ULN at Screening. Exception: if a patient has documented Gilbert's Syndrome, they will be allowed with an elevated bilirubin level per the investigator's discretion.
  14. Has a known history of infection with human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).
  15. If a patient has no known history of HBV infection, then a HBV Screening test panel should be done. If the test is positive and there is clinical manifestation of active infection per Investigator's diagnosis, then the patient should be excluded. In addition, if the patient is considered to need antiviral treatment, the patient should be excluded. (If the test results indicate only an hepatitis B surface antigen (HBsAg) carrier without any clinical manifestation of active infection, and no antiviral treatment is needed, then the patient could be enrolled provided all other criteria are met.)
  16. 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.
  17. Has received any investigational compound within 30 days prior to Screening or has received >7 days of any antidiabetic agent within 3 months prior to Screening.
  18. Has received TAK-875 in a previous clinical study.
  19. Has a history of hypersensitivity, allergies or has had an anaphylactic reaction(s) to any component of TAK-875.
  20. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within 2 years prior to Screening.
  21. Received excluded medications prior to Screening or is expected to receive excluded medications.
  22. If female, is pregnant (confirmed by laboratory testing, ie, serum/urine 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.
  23. If male, intends to donate sperm during the course of this study or for 30 days after final study medication dose.
  24. 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 subject according to the protocol.
  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: NCT01647542

  Hide Study Locations
Locations
Australia, New South Wales
Brookvale, New South Wales, Australia
Maroubra, New South Wales, Australia
Mosman, New South Wales, Australia
Woy Woy, New South Wales, Australia
Australia, South Australia
Elizabeth Vale, South Australia, Australia
China, Anhui
Hefei, Anhui, China
China, Beijing
Beijing, Beijing, China
Beijing,P.R., Beijing, China
China, Chongqing
Chongqing, Chongqing, China
China, Fujian
Fuzhou, Fujian, China
Xiamen, Fujian, China
China, Guangdong
Guangzhou, Guangdong, China
China, Guizhou
Guiyang, Guizhou, China
China, Hebei
Shijiazhuang, Hebei, China
China, Heilongjiang
Harbin, Heilongjiang, China
China, Hubei
Wuhan, Hubei, China
China, Hunan
Changsha, Hunan, China
Chenzhou, Hunan, China
China, Jiangsu
Nanjing, Jiangsu, China
Suzhou, Jiangsu, China
Suzhou City, Jiangsu, China
China, Jilin
Changchun, Jilin, China
Changchun City, Jilin Province, Jilin, China
China, Shaanxi
Xi'an, Shaanxi, China
China, Shanghai
Shanghai, Shanghai, China
China, Shanxi
Xi'an, Shanxi, China
China, Sichuan
Chengdu, Sichuan, China
China, Tianjin
Tianjin, Tianjin, China
China
Beijing, China
Chongqing, China
Guangzhou, China
Guiyang, China
Heilongjiang, China
Nanjing, China
Shanghai, China
Tianjin, China
Korea, Republic of
Goyang-si, Gyeonggi-do, Korea, Republic of
Seongnam-si, Gyeonggi-do, Korea, Republic of
Suwon, Gyeonggi-do, Korea, Republic of
Gyeonggi, Korea, Republic of
Incheon, Korea, Republic of
Seoul, Korea, Republic of
New Zealand
Auckland, New Zealand
Hamilton, New Zealand
Rotorua, New Zealand
Tauranga, New Zealand
Wellington, New Zealand
Taiwan
Kaohsiung, Taiwan
New Taipei City, Taiwan
Taichung, Taiwan
Tainan, Taiwan
Taipei, Taiwan
Taipei City, Taiwan
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01647542     History of Changes
Other Study ID Numbers: TAK-875_307, U1111-1129-7865
Study First Received: July 19, 2012
Last Updated: January 23, 2014
Health Authority: China: Ministry of Health
Australia: National Health and Medical Research Council
New Zealand: Medsafe
Taiwan: Department of Health
Korea: Food and Drug Administration

Keywords provided by Takeda:
Drug therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 21, 2014