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

NCT01549964 | Terminated Phase 3 Results DMC

• 4 other identifiers: TAK-875_3022011-001752-10U1111-1124-2225NMRR-12-446-11314
• Study Type: interventional
• Target: 916
• Locations: 11 countries
• Sites: 160

Brief 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.

Conditions

Glycemic Control

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 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.

  Baseline and Week 24

Secondary Outcomes (2)

• Incidence of HbA1c <7%

  24 Weeks

• Change From Baseline in Fasting Plasma Glucose (FPG)

  Baseline and Week 24

Study Arms (4)

Fasiglifam (TAK-875) 25 mg

EXPERIMENTAL

Fasiglifam 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.

Drug: Fasiglifam (TAK-875)

Fasiglifam (TAK-875) 50 mg

EXPERIMENTAL

Fasiglifam 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.

Drug: Fasiglifam (TAK-875)

Sitagliptin 100 mg

ACTIVE COMPARATOR

Sitagliptin 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.

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

Fasiglifam (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.

Drug: Placebo

Interventions

Fasiglifam (TAK-875) DRUG

Fasiglifam (TAK-875) tablets

Fasiglifam (TAK-875) 25 mg; Fasiglifam (TAK-875) 50 mg

Sitagliptin DRUG

Sitagliptin tablets

Also known as: Januvia

Sitagliptin 100 mg

Placebo DRUG

Placebo-matching tablets

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (160)

Unknown Facility

Muscle Shoals, Alabama, United States

Location

Unknown Facility

Mesa, Arizona, United States

Location

Unknown Facility

Peoria, Arizona, United States

Location

Unknown Facility

Phoenix, Arizona, United States

Location

Unknown Facility

Chula Vista, California, United States

Location

Unknown Facility

El Cajon, California, United States

Location

Unknown Facility

La Mesa, California, United States

Location

Unknown Facility

Laguna Hills, California, United States

Location

Unknown Facility

National City, California, United States

Location

Unknown Facility

Paramount, California, United States

Location

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Stockton, California, United States

Location

Unknown Facility

Tustin, California, United States

Location

Unknown Facility

West Hills, California, United States

Location

Unknown Facility

Trumbull, Connecticut, United States

Location

Unknown Facility

Coral Gables, Florida, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

New Port Richey, Florida, United States

Location

Unknown Facility

Ocala, Florida, United States

Location

Unknown Facility

West Palm Beach, Florida, United States

Location

Unknown Facility

Meridian, Idaho, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Greenfield, Indiana, United States

Location

Unknown Facility

Muncie, Indiana, United States

Location

Unknown Facility

Lexington, Kentucky, United States

Location

Unknown Facility

Owensboro, Kentucky, United States

Location

Unknown Facility

Hyattsville, Maryland, United States

Location

Unknown Facility

Troy, Michigan, United States

Location

Unknown Facility

Picayune, Mississippi, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Haddon Heights, New Jersey, United States

Location

Unknown Facility

Rosedale, New York, United States

Location

Unknown Facility

Calabash, North Carolina, United States

Location

Unknown Facility

Charlotte, North Carolina, United States

Location

Unknown Facility

Monroe, North Carolina, United States

Location

Unknown Facility

Morehead City, North Carolina, United States

Location

Unknown Facility

Winston-Salem, North Carolina, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Dayton, Ohio, United States

Location

Unknown Facility

Norman, Oklahoma, United States

Location

Unknown Facility

Lancaster, Pennsylvania, United States

Location

Unknown Facility

Levittown, Pennsylvania, United States

Location

Unknown Facility

Spartanburg, South Carolina, United States

Location

Unknown Facility

Crossville, Tennessee, United States

Location

Unknown Facility

Memphis, Tennessee, United States

Location

Unknown Facility

Carrollton, Texas, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Irving, Texas, United States

Location

Unknown Facility

Katy, Texas, United States

Location

Unknown Facility

McKinney, Texas, United States

Location

Unknown Facility

Plano, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Spring, Texas, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

West Jordan, Utah, United States

Location

Unknown Facility

Richmond, Virginia, United States

Location

Unknown Facility

Camperdown, New South Wales, Australia

Location

Unknown Facility

Maroubra, New South Wales, Australia

Location

Unknown Facility

Redcliffe, Queensland, Australia

Location

Unknown Facility

Adelaide, South Australia, Australia

Location

Unknown Facility

Daw Park, South Australia, Australia

Location

Unknown Facility

Box Hill, Victoria, Australia

Location

Unknown Facility

Fitzroy, Victoria, Australia

Location

Unknown Facility

Melbourne, Victoria, Australia

Location

Unknown Facility

Byala, Bulgaria

Location

Unknown Facility

Kazanlak, Bulgaria

Location

Unknown Facility

Plovdiv, Bulgaria

Location

Unknown Facility

Sofia, Bulgaria

Location

Unknown Facility

Čakovec, Croatia

Location

Unknown Facility

Karlovac, Croatia

Location

Unknown Facility

Krapinske Toplice, Croatia

Location

Unknown Facility

Rijeka, Croatia

Location

Unknown Facility

Slavonski Brod, Croatia

Location

Unknown Facility

Split, Croatia

Location

Unknown Facility

Zadar, Croatia

Location

Unknown Facility

Zagreb, Croatia

Location

Unknown Facility

Beroun, Czechia

Location

Unknown Facility

Brno, Czechia

Location

Unknown Facility

Havlíčkův Brod, Czechia

Location

Unknown Facility

Kladno, Czechia

Location

Unknown Facility

Kroměříž, Czechia

Location

Unknown Facility

Mladá Boleslav, Czechia

Location

Unknown Facility

Ostrava, Czechia

Location

Unknown Facility

Ostrava - Moravska Ostrava, Czechia

Location

Unknown Facility

Pardubice, Czechia

Location

Unknown Facility

Pilsen, Czechia

Location

Unknown Facility

Písek, Czechia

Location

Unknown Facility

Prague, Czechia

Location

Unknown Facility

Ústí nad Labem, Czechia

Location

Unknown Facility

Baja, Hungary

Location

Unknown Facility

Balatonfüred, Hungary

Location

Unknown Facility

Budaörs, Hungary

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Debrecen, Hungary

Location

Unknown Facility

Eger, Hungary

Location

Unknown Facility

Gödöllő, Hungary

Location

Unknown Facility

Gyöngyös, Hungary

Location

Unknown Facility

Gyula, Hungary

Location

Unknown Facility

Hódmezővásárhely, Hungary

Location

Unknown Facility

Kecskemét, Hungary

Location

Unknown Facility

Kistelek, Hungary

Location

Unknown Facility

Kisvárda, Hungary

Location

Unknown Facility

Komárom, Hungary

Location

Unknown Facility

Mohács, Hungary

Location

Unknown Facility

Nyíregyháza, Hungary

Location

Unknown Facility

Pécs, Hungary

Location

Unknown Facility

Szeged, Hungary

Location

Unknown Facility

Szekszárd, Hungary

Location

Unknown Facility

Szikszó, Hungary

Location

Unknown Facility

Szolnok, Hungary

Location

Unknown Facility

Szombathely, Hungary

Location

Unknown Facility

Úrhida, Hungary

Location

Unknown Facility

Veszprém, Hungary

Location

Unknown Facility

Zalaegerszeg, Hungary

Location

Unknown Facility

Florence, Firenze, Italy

Location

Unknown Facility

Milan, Milano, Italy

Location

Unknown Facility

Sesto San Giovanni, Milano, Italy

Location

Unknown Facility

Pavia, Pavia, Italy

Location

Unknown Facility

Johor Bahru, Johor, Malaysia

Location

Unknown Facility

Alor Star, Kedah, Malaysia

Location

Unknown Facility

Kelantan, Kelantan, Malaysia

Location

Unknown Facility

Kota Bharu, Kelantan, Malaysia

Location

Unknown Facility

Cheras, Kuala Lumpur, Malaysia

Location

Unknown Facility

Kuala Lumpur, Kuala Lumpur, Malaysia

Location

Unknown Facility

Lembah Pantai, Kuala Lumpur, Malaysia

Location

Unknown Facility

Petaling Jaya, Selangor, Malaysia

Location

Unknown Facility

Banská Bystrica, Slovakia

Location

Unknown Facility

Bardejov, Slovakia

Location

Unknown Facility

Bratislava, Slovakia

Location

Unknown Facility

Kosice - Saca, Slovakia

Location

Unknown Facility

Košice, Slovakia

Location

Unknown Facility

Levice, Slovakia

Location

Unknown Facility

Lučenec, Slovakia

Location

Unknown Facility

Moldava nad Bodvou, Slovakia

Location

Unknown Facility

Nitra, Slovakia

Location

Unknown Facility

Pezinok, Slovakia

Location

Unknown Facility

Prešov, Slovakia

Location

Unknown Facility

Prievidza, Slovakia

Location

Unknown Facility

Stropkov, Slovakia

Location

Unknown Facility

Svidník, Slovakia

Location

Unknown Facility

Šahy, Slovakia

Location

Unknown Facility

Štúrovo, Slovakia

Location

Unknown Facility

Trebišov, Slovakia

Location

Unknown Facility

Trenčín, Slovakia

Location

Unknown Facility

Žilina, Slovakia

Location

Unknown Facility

Goyang-si, Gyeonggi-do, South Korea

Location

Unknown Facility

Seongnam-si, Gyeonggi-do, South Korea

Location

Unknown Facility

Incheon, South Korea

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

Bangkok, Bangkok, Thailand

Location

Unknown Facility

Patumwan, Bangkok, Thailand

Location

Unknown Facility

Rachathevi, Bangkok, Thailand

Location

Unknown Facility

Rajtevi, Bangkok, Thailand

Location

Unknown Facility

Ratchathewi, Bangkok, Thailand

Location

Unknown Facility

Khon Kaen, Changwat Khon Kaen, Thailand

Location

Unknown Facility

Muang, Changwat Nakhon Ratchasima, Thailand

Location

Unknown Facility

Hat Yai, Changwat Songkhla, Thailand

Location

Unknown Facility

Muang, Chiang Mai, Thailand

Location

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

Interventions

TAK-875; Sitagliptin Phosphate

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

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

clinicaltrialregistry@tpna.com

+1-877-825-3327

Study Officials

• Senior Medical Director Clinical Science

  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: March 6, 2012
• First Posted: March 9, 2012
• Study Start: April 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: June 2, 2016
• Results First Posted: June 2, 2016

Record last verified: 2016-04

Locations

CZ (13); MY (8); BU (4); IT (4); CR (8); HU (25); KR (4); TH (9); US (58); AU (8); SL (19)