Comparison of Fasiglifam (TAK-875) With Sitagliptin When Used in Combination With Metformin in Patients With Type 2 Diabetes

NCT ID: NCT01834274

Last Updated: 2015-09-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2014-03-31

Brief Summary

The purpose of this study is to evaluate the efficacy of fasiglifam (TAK-875) plus metformin compared with sitagliptin plus metformin on glycemic control over a 24-week Treatment Period.

Detailed Description

The drug being tested in this study is called TAK-875. TAK-875 is being tested to treat people who have type 2 diabetes. This study will look at glycemic control in people who take TAK-875 in addition to metformin.

The study will enroll approximately 620 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 50 mg
• Sitagliptin 100 mg

All participants will be asked to take one tablet at the same time each day throughout the study. All participants will be asked to self-monitor their blood glucose levels and document any increases in blood glucose or symptoms of hypoglycemia in a diary.

This multi-center trial will be conducted in the United States, Latin America, Europe and Asia. The overall time to participate in this study is up to 42 weeks and participants will make up to 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 Mellitus, Type 2

Study Design

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

Study Groups

Fasiglifam 50 mg

Fasiglifam (TAK-875) 50 mg tablets, orally, once daily, Sitagliptin placebo-matching tablets, orally, once daily, and metformin stable dose ≥1500 mg (or maximum-tolerated dose), tablets, orally, daily for up to 24 weeks.

Group Type: EXPERIMENTAL

Fasiglifam (TAK-875)

Intervention Type: DRUG

Fasiglifam (TAK-875) tablets

Sitagliptin Placebo

Intervention Type: DRUG

Sitagliptin placebo-matching tablets

Metformin

Intervention Type: DRUG

Metformin tablets

Sitagliptin 100 mg

Sitagliptin 100 mg, tablets, once daily, TAK-875 placebo-matching tablets, orally, once daily, and metformin stable dose ≥1500 mg (or maximum-tolerated dose), tablets, orally, daily for up to 24 weeks.

Group Type: ACTIVE_COMPARATOR

Fasiglifam (TAK-875) Placebo

Intervention Type: DRUG

Fasiglifam (TAK-875) placebo-matching tablets

Sitagliptin

Intervention Type: DRUG

Sitagliptin tablets

Metformin

Intervention Type: DRUG

Metformin tablets

Interventions

Fasiglifam (TAK-875)

Fasiglifam (TAK-875) tablets

Intervention Type: DRUG

Fasiglifam (TAK-875) Placebo

Fasiglifam (TAK-875) placebo-matching tablets

Intervention Type: DRUG

Sitagliptin

Sitagliptin tablets

Intervention Type: DRUG

Sitagliptin Placebo

Sitagliptin placebo-matching tablets

Intervention Type: DRUG

Metformin

Metformin tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. In the opinion of the investigator, 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. Is male or female and 18 years of age or older with a historical diagnosis of type 2 diabetes mellitus (T2DM).

4. Meets one of the following criteria:.

1. Has an HbA1c ≥8% 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 8 weeks prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;

2. Has an HbA1c ≥8% and <10.5%, and has been on a stable daily dose of <1500 mg of metformin without documented MTD for at least 8 weeks prior to Screening. After completing the Screening Visit, these participants will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8- to 12-week Titration/Stabilization Period according to Study Schedule B. Following stable administration of metformin ≥1500 mg (or MTD) for 8 weeks, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures and have an HbA1c ≥8% and <10.5%.

5. Has had no treatment with anti-diabetic agents other than metformin within 8 weeks prior to Screening (Exception: if a participant has received other anti-diabetic therapy for ≤7 days within the 8 weeks prior to Screening).

6. Has a body mass index (BMI) ≤45 kg/m^2 at Screening.

7. Participants regularly using other, non-excluded medications must be on a stable dose and regimen for at least 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator. Note: Participants who require initiation of a chronically administered medication(s) due to a disease or condition diagnosed at Screening must be rescreened after the new regimen has been stabilized.

8. A female participant of childbearing potential who is sexually active with a non-sterilized 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. Is able and willing to monitor glucose with a sponsor-provided home glucose monitor and consistently record his or her own blood glucose concentrations in diaries.

Exclusion Criteria

1. Has received any investigational compound within 30 days prior to Screening or has received an investigational anti-diabetic drug within the 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) or may consent under duress.

4. Has 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 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening.

6. Has systolic blood pressure ≥160 mm Hg or diastolic blood 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 and decision will be made on the second measurement.)

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

8. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2 x upper limit of normal (ULN) at Screening.

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

10. Has serum creatinine ≥1.5mg/dL (≥133μmol/L) if male or ≥1.4 mg/dL (≥124 μmol/L) if female and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2 at Screening.

11. Has uncontrolled thyroid disease as determined by the investigator.

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

13. Has a history of pancreatitis.

14. Has a history of gastric banding or gastric bypass surgery within one year prior to Screening.

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

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

17. Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of TAK-875, metformin, or 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. Has received excluded medications prior to Screening 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

Role: STUDY_DIRECTOR

Takeda

Locations

Huntsville, Alabama, United States

Chandler, Arizona, United States

Glendale, Arizona, United States

Little Rock, Arkansas, United States

Fresno, California, United States

Garden Grove, California, United States

Modesto, California, United States

San Diego, California, United States

Thousand Oaks, California, United States

Lakewood, Colorado, United States

Hallandale, Florida, United States

Hialeah, Florida, United States

Miami, Florida, United States

Miami Lakes, Florida, United States

North Miami, Florida, United States

North Miami Beach, Florida, United States

Pembroke Pines, Florida, United States

Sanford, Florida, United States

Atlanta, Georgia, United States

Conyers, Georgia, United States

Evans, Georgia, United States

Boise, Idaho, United States

Chicago, Illinois, United States

Evanston, Illinois, United States

Council Bluffs, Iowa, United States

Augusta, Kansas, United States

Omaha, Nebraska, United States

New York, New York, United States

Durham, North Carolina, United States

Greensboro, North Carolina, United States

Hickory, North Carolina, United States

Carlisle, Ohio, United States

Oklahoma City, Oklahoma, United States

Medford, Oregon, United States

Fort Mill, South Carolina, United States

Laurens, South Carolina, United States

Spartanburg, South Carolina, United States

Knoxville, Tennessee, United States

Austin, Texas, United States

Odessa, Texas, United States

San Antonio, Texas, United States

Sugar Land, Texas, United States

Victoria, Texas, United States

Salt Lake City, Utah, United States

Coronel Suárez, Buenos Aires, Argentina

Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

Rosario, Santa Fe Province, Argentina

Calgary, Alberta, Canada

Red Deer, Alberta, Canada

Vancouver, British Columbia, Canada

Victoria, British Columbia, Canada

Winnipeg, Manitoba, Canada

Etobicoke, Ontario, Canada

London, Ontario, Canada

Toronto, Ontario, Canada

Karlovac, , Croatia

Krapinske Toplice, , Croatia

Slavonski Brod, , Croatia

Virovitica, , Croatia

Zagreb, , Croatia

Budapest, , Hungary

Gödöllő, , Hungary

Kistarcsa, , Hungary

Sátoraljaújhely, , Hungary

Szeged, , Hungary

Kelantan, Kelantan, Malaysia

Kuala Lumpur, Kuala Lumpur, Malaysia

Seri Manjung, Perak, Malaysia

Taiping, Perak, Malaysia

Taiping, Perak, Perak, Malaysia

Putrajaya, Selangor, Malaysia

Ica, , Peru

Lima, , Peru

Cebu City, , Philippines

Iloilo City, , Philippines

Marikina City, , Philippines

Pasig, , Philippines

Quezon City, , Philippines

West Fairview, Quezon City, , Philippines

Gdansk, , Poland

Lodz, , Poland

Oświęcim, , Poland

Rzeszów, , Poland

Sobótka, , Poland

Wroclaw, , Poland

Zgierz, , Poland

Barnaul, , Russia

Kemerovo, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Bloemfontein, Free State, South Africa

Pretoria, Gauteng, South Africa

Durban, KwaZulu-Natal, South Africa

Cape Town, Western Cape, South Africa

Bangkoknoi, Bangkok, Thailand

Rajathevee, Bangkok, Thailand

Muang, Changwat Khon Kaen, Thailand

Klongluang, Changwat Pathum Thani, Thailand

Hat Yai, Changwat Songkhla, Thailand

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Vinnytsia, , Ukraine

Countries

United States; Argentina; Canada; Croatia; Hungary; Malaysia; Peru; Philippines; Poland; Russia; South Africa; Thailand; Ukraine

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

2013-000542-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1139-0467

Identifier Type: REGISTRY

Identifier Source: secondary_id

DOH-27-0913-4426

Identifier Type: REGISTRY

Identifier Source: secondary_id

NMRR-13-518-16346

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHRR140127-000165

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-875_310

Identifier Type: -

Identifier Source: org_study_id