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

NCT01834274 | Terminated Phase 3 Results DMC

• 6 other identifiers: TAK-875_3102013-000542-19U1111-1139-0467DOH-27-0913-4426NMRR-13-518-16346PHRR140127-000165
• Study Type: interventional
• Target: 96
• Locations: 13 countries
• Sites: 104

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycosylated Hemoglobin (HbA1c)

  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. A negative change from Baseline indicated improvement.

  Baseline and Week 24

Secondary Outcomes (2)

• Percentage of Participants With HbA1c <7% at Week 24

  Week 24

• Change From Baseline in Fasting Plasma Glucose (FPG)

  Baseline and Week 24

Study Arms (2)

Fasiglifam 50 mg

EXPERIMENTAL

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.

Drug: Fasiglifam (TAK-875); Drug: Sitagliptin Placebo; Drug: Metformin

Sitagliptin 100 mg

ACTIVE COMPARATOR

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.

Drug: Fasiglifam (TAK-875) Placebo; Drug: Sitagliptin; Drug: Metformin

Interventions

Fasiglifam (TAK-875) DRUG

Fasiglifam (TAK-875) tablets

Fasiglifam 50 mg

Fasiglifam (TAK-875) Placebo DRUG

Fasiglifam (TAK-875) placebo-matching tablets

Sitagliptin 100 mg

Sitagliptin DRUG

Sitagliptin tablets

Sitagliptin 100 mg

Sitagliptin Placebo DRUG

Sitagliptin placebo-matching tablets

Fasiglifam 50 mg

Metformin DRUG

Metformin tablets

Fasiglifam 50 mg; Sitagliptin 100 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
• 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.
• Is male or female and 18 years of age or older with a historical diagnosis of type 2 diabetes mellitus (T2DM).
• Meets one of the following criteria:.
• 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;
• 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%.
• 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).
• Has a body mass index (BMI) ≤45 kg/m\^2 at Screening.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Has been randomized into a previous TAK-875 study.
• 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.
• Has donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
• Has a hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening.
• 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.
• Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels \>2 x upper limit of normal (ULN) at Screening.
• 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.
• 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.
• Has uncontrolled thyroid disease as determined by the investigator.
• Has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
• Has a history of pancreatitis.
• Has a history of gastric banding or gastric bypass surgery within one year prior to Screening.
• Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (104)

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Huntsville, Alabama, United States

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Chandler, Arizona, United States

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Glendale, Arizona, United States

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Little Rock, Arkansas, United States

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Fresno, California, United States

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Garden Grove, California, United States

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Modesto, California, United States

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San Diego, California, United States

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Thousand Oaks, California, United States

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Lakewood, Colorado, United States

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Hallandale, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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North Miami, Florida, United States

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North Miami Beach, Florida, United States

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Pembroke Pines, Florida, United States

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Sanford, Florida, United States

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Atlanta, Georgia, United States

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Conyers, Georgia, United States

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Evans, Georgia, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Evanston, Illinois, United States

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Council Bluffs, Iowa, United States

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Augusta, Kansas, United States

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Omaha, Nebraska, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Greensboro, North Carolina, United States

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Hickory, North Carolina, United States

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Carlisle, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Medford, Oregon, United States

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Fort Mill, South Carolina, United States

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Laurens, South Carolina, United States

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Spartanburg, South Carolina, United States

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Knoxville, Tennessee, United States

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Austin, Texas, United States

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Odessa, Texas, United States

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San Antonio, Texas, United States

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Sugar Land, Texas, United States

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Victoria, Texas, United States

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Salt Lake City, Utah, United States

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Coronel Suárez, Buenos Aires, Argentina

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Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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Calgary, Alberta, Canada

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Red Deer, Alberta, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Etobicoke, Ontario, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Karlovac, Croatia

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Krapinske Toplice, Croatia

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Slavonski Brod, Croatia

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Virovitica, Croatia

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Zagreb, Croatia

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Budapest, Hungary

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Gödöllő, Hungary

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Kistarcsa, Hungary

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Sátoraljaújhely, Hungary

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Szeged, Hungary

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Kelantan, Kelantan, Malaysia

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Kuala Lumpur, Kuala Lumpur, Malaysia

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Seri Manjung, Perak, Malaysia

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Taiping, Perak, Malaysia

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Taiping, Perak, Perak, Malaysia

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Putrajaya, Selangor, Malaysia

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Ica, Peru

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Lima, Peru

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Cebu City, Philippines

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Iloilo City, Philippines

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Marikina City, Philippines

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Pasig, Philippines

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Quezon City, Philippines

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West Fairview, Quezon City, Philippines

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Gdansk, Poland

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Lodz, Poland

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Oświęcim, Poland

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Rzeszów, Poland

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Sobótka, Poland

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Wroclaw, Poland

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Zgierz, Poland

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Barnaul, Russia

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Kemerovo, Russia

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Novosibirsk, Russia

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Saint Petersburg, Russia

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Bloemfontein, Free State, South Africa

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Pretoria, Gauteng, South Africa

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Durban, KwaZulu-Natal, South Africa

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Cape Town, Western Cape, South Africa

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Bangkoknoi, Bangkok, Thailand

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Rajathevee, Bangkok, Thailand

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Muang, Changwat Khon Kaen, Thailand

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Klongluang, Changwat Pathum Thani, Thailand

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Hat Yai, Changwat Songkhla, Thailand

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Kyiv, Ukraine

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Lviv, Ukraine

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Vinnytsia, Ukraine

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Related Publications (1)

• 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.

  PMID: 30880443 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

TAK-875; Sitagliptin Phosphate; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: June 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: September 28, 2015
• Results First Posted: September 28, 2015

Record last verified: 2015-08

Locations

US (44); MY (6); CA (8); ZA (4); TH (5); UA (5); CR (5); PE (2); AR (3); HU (5); PH (6); RU (4); PL (7)