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Glycemic ControlPhase 3NCT01549964

Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes

A Phase 3 study testing Fasiglifam (TAK-875) and Sitagliptin in people with Glycemic Control, run by Takeda at 160 sites in 11 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 2 doses of TAK-875 (25 mg and 50 mg), once daily (QD), plus metformin compared to placebo plus metformin and sitagliptin plus metformin on lowering blood sugar. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glycemic Control
What is being tested?
Fasiglifam (TAK-875) and Sitagliptin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
916 participants
Where
160 sitesin 11 countries
Study dates
Apr 2012to 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

  • The participant is male or female and 18 years of age or older with a historical diagnosis of type II diabetes mellitus.
  • The participant meets one of the following criteria:
  • The participant has an HbA1c level ≥7.5 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 2 months prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;
  • The participant has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of <1500 mg of metformin without documented MTD for at least 2 months prior to Screening. After completing the Screening Visit, this participant will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8-week Titration Period according to Study Schedule B. Following this 8-week period, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures including having an HbA1c level ≥7.5 and <10.5%.
  • The participant has had no treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for ≤7 days within the 2 months prior to Screening).
  • The participant has a body mass index (BMI) ≤45 kg/m² at Screening.
  • 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 medications is allowed at the discretion of the investigator.
  • 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 subject diaries.

Who cannot join

  • The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
  • Hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening Visit.
  • The participant has systolic blood pressure ≥160 mm Hg or diastolic 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.)
  • The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
  • The participant has had treatment for gastric banding or gastric bypass surgery within one year prior to Screening.
  • The participant had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.

Trial locations and contacts

160 sites in 11 countries.

160 sites in 11 countries

United States58 sites

  • Study site

    Calabash, North Carolina

  • Study site

    Carrollton, Texas

  • Study site

    Charlotte, North Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Chula Vista, California

  • Study site

    Cincinnati, Ohio

  • Study site

    Cleveland, Ohio

  • Study site

    Coral Gables, Florida

  • Study site

    Crossville, Tennessee

  • Study site

    Dayton, Ohio

  • Study site

    El Cajon, California

  • Study site

    Greenfield, Indiana

  • Study site

    Haddon Heights, New Jersey

  • Study site

    Houston, Texas

  • Study site

    Hyattsville, Maryland

  • Study site

    Irving, Texas

  • Study site

    Jacksonville, Florida

  • Study site

    Katy, Texas

  • Study site

    La Mesa, California

  • Study site

    Laguna Hills, California

  • Study site

    Lancaster, Pennsylvania

  • Study site

    Levittown, Pennsylvania

  • Study site

    Lexington, Kentucky

  • Study site

    McKinney, Texas

  • Study site

    Memphis, Tennessee

  • Study site

    Meridian, Idaho

  • Study site

    Mesa, Arizona

  • Study site

    Miami, Florida

  • Study site

    Monroe, North Carolina

  • Study site

    Morehead City, North Carolina

  • Study site

    Muncie, Indiana

  • Study site

    Muscle Shoals, Alabama

  • Study site

    National City, California

  • Study site

    New Port Richey, Florida

  • Study site

    Norman, Oklahoma

  • Study site

    Ocala, Florida

  • Study site

    Owensboro, Kentucky

  • Study site

    Paramount, California

  • Study site

    Peoria, Arizona

  • Study site

    Phoenix, Arizona

  • Study site

    Picayune, Mississippi

  • Study site

    Plano, Texas

  • Study site

    Richmond, Virginia

  • Study site

    Rosedale, New York

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    Spartanburg, South Carolina

  • Study site

    Spring, Texas

  • Study site

    St Louis, Missouri

  • Study site

    Stockton, California

  • Study site

    Troy, Michigan

  • Study site

    Trumbull, Connecticut

  • Study site

    Tustin, California

  • Study site

    West Hills, California

  • Study site

    West Jordan, Utah

  • Study site

    West Palm Beach, Florida

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Hungary25 sites

  • Study site

    Baja

  • Study site

    Balatonfüred

  • Study site

    Budaörs

  • Study site

    Budapest

  • Study site

    Debrecen

  • Study site

    Eger

  • Study site

    Gödöllő

  • Study site

    Gyöngyös

  • Study site

    Gyula

  • Study site

    Hódmezővásárhely

  • Study site

    Kecskemét

  • Study site

    Kistelek

  • Study site

    Kisvárda

  • Study site

    Komárom

  • Study site

    Mohács

  • Study site

    Nyíregyháza

  • Study site

    Pécs

  • Study site

    Szeged

  • Study site

    Szekszárd

  • Study site

    Szikszó

  • Study site

    Szolnok

  • Study site

    Szombathely

  • Study site

    Úrhida

  • Study site

    Veszprém

  • Study site

    Zalaegerszeg

Other trials in Hungary

Slovakia19 sites

  • Study site

    Banská Bystrica

  • Study site

    Bardejov

  • Study site

    Bratislava

  • Study site

    Košice

  • Study site

    Kosice - Saca

  • Study site

    Levice

  • Study site

    Lučenec

  • Study site

    Moldava nad Bodvou

  • Study site

    Nitra

  • Study site

    Pezinok

  • Study site

    Prešov

  • Study site

    Prievidza

  • Study site

    Šahy

  • Study site

    Stropkov

  • Study site

    Štúrovo

  • Study site

    Svidník

  • Study site

    Trebišov

  • Study site

    Trenčín

  • Study site

    Žilina

Other trials in Slovakia

Czechia13 sites

  • Study site

    Beroun

  • Study site

    Brno

  • Study site

    Havlíčkův Brod

  • Study site

    Kladno

  • Study site

    Kroměříž

  • Study site

    Mladá Boleslav

  • Study site

    Ostrava

  • Study site

    Ostrava - Moravska Ostrava

  • Study site

    Pardubice

  • Study site

    Pilsen

  • Study site

    Písek

  • Study site

    Prague

  • Study site

    Ústí nad Labem

Other trials in Czechia

Thailand9 sites

  • Study site

    Bangkok, Bangkok

  • Study site

    Hat Yai, Changwat Songkhla

  • Study site

    Khon Kaen, Changwat Khon Kaen

  • Study site

    Muang, Changwat Nakhon Ratchasima

  • Study site

    Muang, Chiang Mai

  • Study site

    Patumwan, Bangkok

  • Study site

    Rachathevi, Bangkok

  • Study site

    Rajtevi, Bangkok

  • Study site

    Ratchathewi, Bangkok

Other trials in Thailand

Australia8 sites

  • Study site

    Adelaide, South Australia

  • Study site

    Box Hill, Victoria

  • Study site

    Camperdown, New South Wales

  • Study site

    Daw Park, South Australia

  • Study site

    Fitzroy, Victoria

  • Study site

    Maroubra, New South Wales

  • Study site

    Melbourne, Victoria

  • Study site

    Redcliffe, Queensland

Other trials in Australia

Croatia8 sites

  • Study site

    Čakovec

  • Study site

    Karlovac

  • Study site

    Krapinske Toplice

  • Study site

    Rijeka

  • Study site

    Slavonski Brod

  • Study site

    Split

  • Study site

    Zadar

  • Study site

    Zagreb

Other trials in Croatia

Malaysia8 sites

  • Study site

    Alor Star, Kedah

  • Study site

    Cheras, Kuala Lumpur

  • Study site

    Johor Bahru, Johor

  • Study site

    Kelantan, Kelantan

  • Study site

    Kota Bharu, Kelantan

  • Study site

    Kuala Lumpur, Kuala Lumpur

  • Study site

    Lembah Pantai, Kuala Lumpur

  • Study site

    Petaling Jaya, Selangor

Other trials in Malaysia

Bulgaria4 sites

  • Study site

    Byala

  • Study site

    Kazanlak

  • Study site

    Plovdiv

  • Study site

    Sofia

Other trials in Bulgaria

Italy4 sites

  • Study site

    Florence, Firenze

  • Study site

    Milan, Milano

  • Study site

    Pavia, Pavia

  • Study site

    Sesto San Giovanni, Milano

Other trials in Italy

South Korea4 sites

  • Study site

    Goyang-si, Gyeonggi-do

  • Study site

    Incheon

  • Study site

    Seongnam-si, Gyeonggi-do

  • Study site

    Seoul

Other trials in South Korea

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-875 25 mg and 50 mg Compared to Placebo and 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 2 doses of TAK-875 (25 mg and 50 mg), once daily (QD), plus metformin compared to placebo plus metformin and sitagliptin plus metformin on lowering blood sugar.

Read the detailed description

TAK-875 is being developed at Takeda Development Center, Inc. as an adjunct to diet and exercise to improve glycemic control in participants with Type 2 Diabetes Mellitus (T2DM) whose blood glucose level is inadequately controlled with metformin.

This study will evaluate the efficacy of TAK-875 (25 mg and 50 mg) plus metformin compared to placebo plus metformin and sitagliptin plus metformin on glycemic control as measured by change from baseline in glycosylated hemoglobin (HbA1c) over a 24-week Treatment Period. Participants completing the 24-week Treatment Period may enter an optional 80-week extension period for a total of 104 weeks of treatment.

Due to concerns about potential 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), Sitagliptin, Placebo
Keywords
Drug Therapy

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

  • SitagliptinDrug

    Also called Januvia

    Sitagliptin tablets

  • PlaceboDrug

    Placebo-matching tablets

Study groups in NCT01549964
Study groupRoleWhat they receive
Fasiglifam (TAK-875) 25 mgExperimentalFasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Receives: Drug: Fasiglifam (TAK-875)
Fasiglifam (TAK-875) 50 mgExperimentalFasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Receives: Drug: Fasiglifam (TAK-875)
Sitagliptin 100 mgActive comparatorSitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. TAK-875 placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Receives: Drug: Sitagliptin
PlaceboPlacebo comparatorFasiglifam (TAK-875) placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Receives: Drug: Placebo

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 relative to Baseline. A Mixed Model Repeated Measures (MMRM) model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.

    Measured: Baseline and Week 24

Secondary outcomes (2)

  1. Incidence of HbA1c <7%

    Incidence (percentage) of participants with glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than 7% at Week 24.

    Measured: 24 Weeks

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

    The change between FPG collected at week 24 relative to Baseline. A MMRM model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.

    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 posted9 Mar 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionMar 2014
  4. Study completionMar 2014

Why it stopped: Due to concerns about potential 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
916 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01549964
Sponsor's protocol ID
TAK-875_302
Other IDs
2011-001752-10, U1111-1124-2225, NMRR-12-446-11314
Status last verified
Apr 2016
First submitted
6 Mar 2012
Last updated
2 Jun 2016
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) and Sitagliptin in people with Glycemic Control, run by Takeda at 160 sites in 11 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 8 inclusion and 6 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 2 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 160 sites in United States, Hungary, Slovakia, Czechia, Thailand and 6 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. Some participants in this study may receive a placebo. 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 2 Jun 2016). 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 NCT01549964, 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 2 Jun 2016.

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