TAK-875 (Fasiglifam) in Combination With Sitagliptin in Adults With Type 2 Diabetes

NCT ID: NCT01829464

Last Updated: 2016-06-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2014-03-31

Brief Summary

The purpose of this study is to evaluate the effect of TAK-875 (fasiglifam) in combination with sitagliptin on glycemic control in adults with type 2 diabetes.

Detailed Description

The drug being tested in this study is called TAK-875 (fasiglifam). Fasiglifam is being tested to treat people who have type 2 diabetes mellitus and are currently taking sitagliptin (with or without metformin). This study will evaluate glycemic control in people who take fasiglifam plus sitagliptin compared with placebo plus sitagliptin.

The study will enroll approximately 390 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need; all participants will be on 100 mg sitagliptin and may or may not be on metformin background treatment):

• fasiglifam 25 mg
• fasiglifam 50 mg
• 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.

This multi-centre trial will be conducted in North America and Latin America. The overall time to participate in this study is approximately 38 weeks. Participants will make 15 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.

Conditions

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

TAK-875 placebo-matching tablets, orally, once daily and sitagliptin 100 mg, tablets, orally for up 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TAK-875 placebo-matching tablets

TAK-875 25 mg

TAK-875 25 mg, tablets, orally, once daily and sitagliptin 100 mg, tablets, orally for up to 24 weeks

Group Type: EXPERIMENTAL

TAK-875

Intervention Type: DRUG

TAK-875 tablets

TAK-875 50 mg

TAK-875 50 mg, tablets, orally, once daily and sitagliptin 100 mg, tablets, orally for up to 24 weeks

Group Type: EXPERIMENTAL

TAK-875

Intervention Type: DRUG

TAK-875 tablets

Interventions

Placebo

TAK-875 placebo-matching tablets

Intervention Type: DRUG

TAK-875

TAK-875 tablets

Intervention Type: DRUG

TAK-875

TAK-875 tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant'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. The participant is male or female and aged 18 years or older with a historical diagnosis of T2DM.

4. The participant meets one of the following criteria:

• The participant has an HbA1c between 7.5% and 10.5%, inclusive and has been taking a stable dose of sitagliptin 100 mg for at least 8 weeks, with or without metformin, prior to the Screening Visit. A participant who is taking metformin must have received a stable daily dose (≥1500 mg or documented maximum tolerated dose [MTD]) for at least 8 weeks before Screening. This participant will enter the 2-week single-blind Placebo Run-In Period according to Study Schedule A, or;

Exclusion Criteria

Note: An enrollment cap may be applied to ensure no more than approximately 20% of randomized participants are receiving a DPP-IV inhibitor without metformin at baseline.

5. The participant has had no treatment with antidiabetic agents other than DPP-IV inhibitors and metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for ≤7 consecutive days within the 2 months prior to Screening).

6. The participant has a body mass index (BMI) ≤45 kg/m2 at Screening.

7. 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 medication is allowed at the discretion of the investigator.

8. A female participant 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.

9. 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 participant diaries.

1. Has received any investigational compound within 30 days prior to Screening or has received an investigational antidiabetic drug within 3 months prior to Screening.

2. Has been randomized into a previous TAK-875 study.

3. 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.

4. Donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.

5. Has a hemoglobin ≤12 g/dL (≤120 gm/L) for males and ≤10 g/dL (≤100 gm/L) for females at the Screening Visit.

7. Has history of cancer that has been in remission for <5 years prior to Screening. (Exception: A history of basal cell carcinoma or stage 1 squamous cell carcinoma of the skin is allowed.)

8. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2.0x the upper limit of normal (ULN) at Screening.

9. Has a total bilirubin level greater than the ULN at Screening. Exception: if a participant has documented Gilbert's Syndrome, they will be allowed with an elevated bilirubin level per the investigator's discretion.

10. Has a serum creatinine ≥1.5 mg/dL (≥133 μmol/L) [males] and ≥1.4 mg/dL (≥124 μmol/L) [females] and/or estimated glomerular filtration rate (GFR) <60 mL/min/1.73m^2 at Screening.

11. Has uncontrolled thyroid disease.

12. Has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.

13. Has had gastric banding or gastric bypass surgery within one year prior to Screening.

14. Has a known history of infection with human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).

15. Had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal electrocardiogram (ECG), cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.

16. Has a history of pancreatitis.

17. Has a history of hypersensitivity, allergies or has had an anaphylactic reaction(s) to any component of TAK-875 as well as sitagliptin.

18. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.

19. Received excluded medications prior to the Screening Visit or is expected to receive excluded medications.

20. 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.

21. Is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.

22. 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 participant according to the protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director, MD

Role: STUDY_DIRECTOR

Takeda

Locations

Birmingham, Alabama, United States

Dothan, Alabama, United States

Muscle Shoals, Alabama, United States

Phoenix, Arizona, United States

Anaheim, California, United States

El Cajon, California, United States

Long Beach, California, United States

Modesto, California, United States

North Hollywood, California, United States

Norwalk, California, United States

Pismo Beach, California, United States

San Diego, California, United States

Vista, California, United States

West Hills, California, United States

Boca Raton, Florida, United States

Boynton Beach, Florida, United States

Bradenton, Florida, United States

Clearwater, Florida, United States

Cocoa, Florida, United States

Doral, Florida, United States

Miami, Florida, United States

North Miami, Florida, United States

Pembroke Pines, Florida, United States

Port Orange, Florida, United States

Tampa, Florida, United States

West Palm Beach, Florida, United States

Atlanta, Georgia, United States

Savannah, Georgia, United States

Woodstock, Georgia, United States

Boise, Idaho, United States

Meridian, Idaho, United States

Apex Medical Research, MI, Inc

Chicago, Illinois, United States

Chicago, Illinois, United States

Avon, Indiana, United States

Greenfield, Indiana, United States

Muncie, Indiana, United States

Council Bluffs, Iowa, United States

Topeka, Kansas, United States

Owensboro, Kentucky, United States

Oxon Hill, Maryland, United States

Fall River, Massachusetts, United States

St Louis, Missouri, United States

Washington, Missouri, United States

Omaha, Nebraska, United States

Nashua, New Hampshire, United States

Elizabeth, New Jersey, United States

Haddon Heights, New Jersey, United States

Albany, New York, United States

Rosedale, New York, United States

Calabash, North Carolina, United States

Charlotte, North Carolina, United States

Greensboro, North Carolina, United States

Morganton, North Carolina, United States

Winston-Salem, North Carolina, United States

Dayton, Ohio, United States

Maumee, Ohio, United States

Norman, Oklahoma, United States

Oklahoma City, Oklahoma, United States

Feasterville, Pennsylvania, United States

Harleysville, Pennsylvania, United States

Levittown, Pennsylvania, United States

Uniontown, Pennsylvania, United States

Fort Mill, South Carolina, United States

Greer, South Carolina, United States

Spartanburg, South Carolina, United States

Crossville, Tennessee, United States

Knoxville, Tennessee, United States

Carrollton, Texas, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Irving, Texas, United States

Katy, Texas, United States

Lewisville, Texas, United States

McKinney, Texas, United States

New Braunfels, Texas, United States

Plano, Texas, United States

San Antonio, Texas, United States

Tomball, Texas, United States

Salt Lake City, Utah, United States

Burke, Virginia, United States

Manassas, Virginia, United States

Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

Salta, Salta Province, Argentina

Rosario, Santa Fe Province, Argentina

Lima, , Peru

Countries

United States; Argentina; Peru

References

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.

Reference Type: DERIVED

PMID: 30880443 (View on PubMed)

Other Identifiers

U1111-1124-2270

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-875_303

Identifier Type: -

Identifier Source: org_study_id