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Diabetes Mellitus, Type 2Phase 3NCT01834274

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

A Phase 3 study testing Fasiglifam (TAK-875), Sitagliptin and Metformin in people with Diabetes Mellitus, Type 2, run by Takeda at 104 sites in 13 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Fasiglifam (TAK-875), Sitagliptin and Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
96 participants
Where
104 sitesin 13 countries
Study dates
Jun 2013to Mar 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%.
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  • 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.

Who cannot join

  • 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 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.)
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  • 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.
  • Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of TAK-875, metformin, or sitagliptin.
  • Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
  • Has received excluded medications prior to Screening or is expected to receive excluded medications.
  • 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.
  • Is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.
  • 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.

Trial locations and contacts

104 sites in 13 countries.

104 sites in 13 countries

United States44 sites

  • Study site

    Atlanta, Georgia

  • Study site

    Augusta, Kansas

  • Study site

    Austin, Texas

  • Study site

    Boise, Idaho

  • Study site

    Carlisle, Ohio

  • Study site

    Chandler, Arizona

  • Study site

    Chicago, Illinois

  • Study site

    Conyers, Georgia

  • Study site

    Council Bluffs, Iowa

  • Study site

    Durham, North Carolina

  • Study site

    Evans, Georgia

  • Study site

    Evanston, Illinois

  • Study site

    Fort Mill, South Carolina

  • Study site

    Fresno, California

  • Study site

    Garden Grove, California

  • Study site

    Glendale, Arizona

  • Study site

    Greensboro, North Carolina

  • Study site

    Hallandale, Florida

  • Study site

    Hialeah, Florida

  • Study site

    Hickory, North Carolina

  • Study site

    Huntsville, Alabama

  • Study site

    Knoxville, Tennessee

  • Study site

    Lakewood, Colorado

  • Study site

    Laurens, South Carolina

  • Study site

    Little Rock, Arkansas

  • Study site

    Medford, Oregon

  • Study site

    Miami, Florida

  • Study site

    Miami Lakes, Florida

  • Study site

    Modesto, California

  • Study site

    New York, New York

  • Study site

    North Miami, Florida

  • Study site

    North Miami Beach, Florida

  • Study site

    Odessa, Texas

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Omaha, Nebraska

  • Study site

    Pembroke Pines, Florida

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    Sanford, Florida

  • Study site

    Spartanburg, South Carolina

  • Study site

    Sugar Land, Texas

  • Study site

    Thousand Oaks, California

  • Study site

    Victoria, Texas

Other trials in United States

Canada8 sites

  • Study site

    Calgary, Alberta

  • Study site

    Etobicoke, Ontario

  • Study site

    London, Ontario

  • Study site

    Red Deer, Alberta

  • Study site

    Toronto, Ontario

  • Study site

    Vancouver, British Columbia

  • Study site

    Victoria, British Columbia

  • Study site

    Winnipeg, Manitoba

Other trials in Canada

Poland7 sites

  • Study site

    Gdansk

  • Study site

    Lodz

  • Study site

    Oświęcim

  • Study site

    Rzeszów

  • Study site

    Sobótka

  • Study site

    Wroclaw

  • Study site

    Zgierz

Other trials in Poland

Malaysia6 sites

  • Study site

    Kelantan, Kelantan

  • Study site

    Kuala Lumpur, Kuala Lumpur

  • Study site

    Putrajaya, Selangor

  • Study site

    Seri Manjung, Perak

  • Study site

    Taiping, Perak

  • Study site

    Taiping, Perak, Perak

Other trials in Malaysia

Philippines6 sites

  • Study site

    Cebu City

  • Study site

    Iloilo City

  • Study site

    Marikina City

  • Study site

    Pasig

  • Study site

    Quezon City

  • Study site

    West Fairview, Quezon City

Other trials in Philippines

Croatia5 sites

  • Study site

    Karlovac

  • Study site

    Krapinske Toplice

  • Study site

    Slavonski Brod

  • Study site

    Virovitica

  • Study site

    Zagreb

Other trials in Croatia

Hungary5 sites

  • Study site

    Budapest

  • Study site

    Gödöllő

  • Study site

    Kistarcsa

  • Study site

    Sátoraljaújhely

  • Study site

    Szeged

Other trials in Hungary

Thailand5 sites

  • Study site

    Bangkoknoi, Bangkok

  • Study site

    Hat Yai, Changwat Songkhla

  • Study site

    Klongluang, Changwat Pathum Thani

  • Study site

    Muang, Changwat Khon Kaen

  • Study site

    Rajathevee, Bangkok

Other trials in Thailand

Ukraine5 sites

  • Study site

    Ivano-Frankivsk

  • Study site

    Kharkiv

  • Study site

    Kyiv

  • Study site

    Lviv

  • Study site

    Vinnytsia

Other trials in Ukraine

Russia4 sites

  • Study site

    Barnaul

  • Study site

    Kemerovo

  • Study site

    Novosibirsk

  • Study site

    Saint Petersburg

Other trials in Russia

South Africa4 sites

  • Study site

    Bloemfontein, Free State

  • Study site

    Cape Town, Western Cape

  • Study site

    Durban, KwaZulu-Natal

  • Study site

    Pretoria, Gauteng

Other trials in South Africa

Argentina3 sites

  • Study site

    Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires

  • Study site

    Coronel Suárez, Buenos Aires

  • Study site

    Rosario, Santa Fe Province

Other trials in Argentina

Peru2 sites

  • Study site

    Ica

  • Study site

    Lima

Other trials in Peru

About this study

Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, 24-Week Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 50 mg Compared With Sitagliptin 100 mg When Used in Combination With Metformin in Subjects With Type 2 Diabetes

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.

Read the 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.

Being tested
Fasiglifam (TAK-875), Fasiglifam (TAK-875) Placebo, Sitagliptin, Sitagliptin Placebo, Metformin
Keywords
Drug Therapy
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fasiglifam (TAK-875)Drug

    Fasiglifam (TAK-875) tablets

  • Fasiglifam (TAK-875) PlaceboDrug

    Fasiglifam (TAK-875) placebo-matching tablets

  • SitagliptinDrug

    Sitagliptin tablets

  • Sitagliptin PlaceboDrug

    Sitagliptin placebo-matching tablets

  • MetforminDrug

    Metformin tablets

Study groups in NCT01834274
Study groupRoleWhat they receive
Fasiglifam 50 mgExperimentalFasiglifam (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.
Receives: Drug: Fasiglifam (TAK-875); Drug: Sitagliptin Placebo; Drug: Metformin
Sitagliptin 100 mgActive comparatorSitagliptin 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.
Receives: Drug: Fasiglifam (TAK-875) Placebo; Drug: Sitagliptin; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and Week 24

Secondary outcomes (2)

  1. Percentage of Participants With HbA1c <7% at Week 24

    The percentage of participants with glycosylated hemoglobin less than 7% after 24 weeks of treatment.

    Measured: Week 24

  2. Change From Baseline in Fasting Plasma Glucose (FPG)

    The change between FPG collected at week 24 or final visit relative to Baseline. A negative change from Baseline indicated improvement.

    Measured: Baseline and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2013 (estimated)
  2. Study startJun 2013
  3. Primary completionMar 2014
  4. Study completionMar 2014

Why it stopped: Due to potential concerns about liver safety (See Detailed Description)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01834274
Sponsor's protocol ID
TAK-875_310
Other IDs
2013-000542-19, U1111-1139-0467, DOH-27-0913-4426, NMRR-13-518-16346, PHRR140127-000165
Status last verified
Aug 2015
First submitted
12 Apr 2013
Last updated
28 Sep 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 30880443

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fasiglifam (TAK-875), Sitagliptin and Metformin in people with Diabetes Mellitus, Type 2, run by Takeda at 104 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 104 sites in United States, Canada, Poland, Malaysia, Philippines and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Glycosylated Hemoglobin (HbA1c) (time frame: Baseline and Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01834274, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2015.

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