Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Patients With Type 2 Diabetes Mellitus

NCT ID: NCT00856284

Last Updated: 2013-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2639 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2012-10-31

Brief Summary

The purpose of this study is to determine the safety and effectiveness of adding alogliptin, once daily (QD), compared to glipizide with metformin in diabetic patients.

Detailed Description

For patients diagnosed with type 2 diabetes mellitus, metformin is the usual first-line therapy in addition to diet control and exercise. For those patients with inadequate glycemic control with metformin monotherapy or experiencing serious side effects of metformin, sulfonylurea is a popular choice as a second-line oral antidiabetic treatment.

Alogliptin is a dipeptidyl peptidase-4 inhibitor currently being developed by Takeda for use in patients with type 2 diabetes mellitus.

This study is designed to further explore the durability of efficacy and safety of alogliptin compared to glipizide in type 2 diabetes mellitus patients whose blood sugar level is inadequately controlled with metformin therapy.

The duration of this study will be approximately 2 years.

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes Mellitus; Drug Therapy; Hyperinsulinism; Hyperglycemia; Glucose Intolerance

Study Design

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

Study Groups

Metformin + Alogliptin 12.5 mg

Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin tablets

Metformin

Intervention Type: DRUG

Metformin tablets

Metformin + Alogliptin 25 mg

Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin tablets

Metformin

Intervention Type: DRUG

Metformin tablets

Metformin + Glipizide

Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin tablets

Glipizide

Intervention Type: DRUG

Glipizide tablets

Interventions

Alogliptin

Alogliptin tablets

Intervention Type: DRUG

Metformin

Metformin tablets

Intervention Type: DRUG

Glipizide

Glipizide tablets

Intervention Type: DRUG

Other Intervention Names

SYR-322; Nesina; Glucophage; Glucotrol

Eligibility Criteria

Inclusion Criteria

• Has a diagnosis of type 2 diabetes mellitus.
• Must meet one of the following:

• Has been inadequately controlled on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose) of metformin for at least 2 months prior to Screening.
• Has been inadequately controlled (as defined by a glycosylated hemoglobin 7.5 - 10%, inclusive) on metformin <1500 mg without documented maximum tolerated dose.
• No treatment with antidiabetic agents other than metformin within 2 months prior to Screening (for Schedule A)/Pre-Screening (for Schedule B).
• Has body mass index within 23 kg/m^2 and 45 kg/m^2 unless the patient is Asian or of Asian descent, for whom the allowable body mass index will be ≥ 20 kg/m^2 and ≤ 35 kg/m^2, inclusive.
• Has fasting C-peptide concentration at least 0.8 ng.
• If regularly using non-excluded medications, must be on a stable dose at least 4 weeks prior to Screening/Pre-screening.
• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant, lactating or intends to donate ova from Screening throughout the duration of the study.
• Must be able and willing to monitor their blood glucose concentrations with a home monitor, and comply with protocol requirements including scheduled clinic appointments.

Exclusion Criteria

• Systolic blood pressure greater than or equal to 150 mmHg and/or diastolic pressure greater than or equal to 90.
• Hemoglobin less than or equal to 12 g/dL for males and less than or equal to 10 g/dL for females at Screening Visit.
• Alanine aminotransferase greater than or equal to 2.5 times the upper limit of normal at Screening Visit.
• Serum creatinine greater than or equal to 1.5 mg/dL for males and 1.4 for females, or calculated creatinine clearance less than 60 L/min.
• Males intending to impregnate others or donate sperm before, during or within 1 month after participating in the study.
• A history of cancer other than squamous or basal cell carcinoma of the skin that has not been in full remission for at least 5 years.
• A history of laser treatment for diabetic retinopathy within 6 months of screening.
• Treated for diabetic gastric paresis, gastric banding, or gastric bypass.
• New York Heart Association Class III or IV heart failure.
• History of coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, stroke or transient ischemic attack within 3 months prior to screening.
• Known history of human immunodeficiency virus, hepatitis B or C.
• Alcohol or substance abuse within 2 years prior to screening.
• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

• Any investigational drug within 30 days
• Any investigational diabetic drug within 3 months
• Any antidiabetic drug in the dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 mimetics classes within 90 days prior to Screening other than metformin
• Prior treatment with alogliptin.
• Weight-loss drugs
• Oral or systemically injected glucocorticoids
• A hypersensitivity allergy or anaphylactic reaction to any dipeptidyl peptidase-4 drug, metformin or glipizide.
• Has a documented history or concurrent signs of significant thyroid disease (eg, autoimmune thyroid diseases such as Graves disease and Hashimoto thyroiditis or active thyroid nodules).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director, Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Montgomery, Alabama, United States

Muscle Shoals, Alabama, United States

Pell City, Alabama, United States

Mesa, Arizona, United States

Peoria, Arizona, United States

Phoenix, Arizona, United States

Sierra Vista, Arizona, United States

Tempe, Arizona, United States

Tucson, Arizona, United States

Anaheim, California, United States

Artesia, California, United States

Chico, California, United States

Los Alamitos, California, United States

Mission Viejo, California, United States

National City, California, United States

Northridge, California, United States

Pismo Beach, California, United States

Riverside, California, United States

Roseville, California, United States

Sacramento, California, United States

San Diego, California, United States

Santa Monica, California, United States

Tustin, California, United States

Arvada, Colorado, United States

Colorado Springs, Colorado, United States

Ridgefield, Connecticut, United States

Waterbury, Connecticut, United States

Brooksville, Florida, United States

New Port Richey, Florida, United States

North Miami Beach, Florida, United States

Ocala, Florida, United States

Opa-locka, Florida, United States

Orlando, Florida, United States

Augusta, Georgia, United States

Savannah, Georgia, United States

Addison, Illinois, United States

Chicago, Illinois, United States

Bloomington, Indiana, United States

Evansville, Indiana, United States

Indianapolis, Indiana, United States

Mishawaka, Indiana, United States

South Bend, Indiana, United States

Lexington, Kentucky, United States

Munfordville, Kentucky, United States

Marrero, Louisiana, United States

Bangor, Maine, United States

Elkridge, Maryland, United States

Oxon Hill, Maryland, United States

North Dartmouth, Massachusetts, United States

Ann Arbor, Michigan, United States

Flint, Michigan, United States

Picayune, Mississippi, United States

City of Saint Peters, Missouri, United States

Springfield, Missouri, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Las Vegas, Nevada, United States

Albuquerque, New Mexico, United States

New Windsor, New York, United States

New York, New York, United States

Rochester, New York, United States

Fargo, North Dakota, United States

Beachwood, Ohio, United States

Cincinnati, Ohio, United States

Dayton, Ohio, United States

Willoughby Hills, Ohio, United States

Zanesville, Ohio, United States

Norman, Oklahoma, United States

Oklahoma City, Oklahoma, United States

Medford, Oregon, United States

Havertown, Pennsylvania, United States

Norristown, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Tipton, Pennsylvania, United States

Anderson, South Carolina, United States

Charleston, South Carolina, United States

Greer, South Carolina, United States

Rapid City, South Dakota, United States

New Tazewell, Tennessee, United States

Arlington, Texas, United States

Carrollton, Texas, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Hurst, Texas, United States

Katy, Texas, United States

San Antonio, Texas, United States

Spring, Texas, United States

Temple, Texas, United States

Midvale, Utah, United States

Hampton, Virginia, United States

Lewisburg, West Virginia, United States

Milwaukee, Wisconsin, United States

Mar del Plata, , Argentina

Garran, Australian Capital Territory, Australia

Wollongong, New South Wales, Australia

Herston, Queensland, Australia

Nedlands, Western Australia, Australia

Graz, , Austria

Salzburg, , Austria

Recife, Pernambuco, Brazil

Brasília - DF, Planalto Central, Brazil

Mogi das Cruzes, São Paulo, Brazil

São Paulo, São Paulo, Brazil

Fortaleza, , Brazil

St. John's, Newfoundland and Labrador, Canada

Brampton, Ontario, Canada

Collingwood, Ontario, Canada

Corunna, Ontario, Canada

Etobichoke, Ontario, Canada

Etobicoke, Ontario, Canada

Mississauga, Ontario, Canada

Smith Falls, Ontario, Canada

Smiths Falls, Ontario, Canada

Toronto, Ontario, Canada

Granby, Quebec, Canada

Montreal, Quebec, Canada

Providencia, Santiago Metropolitan, Chile

Santiago, Santiago Metropolitan, Chile

Potsdam, Brandenburg, Germany

Kelkheim, Hesse, Germany

Offenbach, Hesse, Germany

Münster, North Rhine-Westphalia, Germany

Mainz, Rhineland-Palatinate, Germany

Neuwied, Rhineland-Palatinate, Germany

Rhaunen, Rhineland-Palatinate, Germany

Guatemala City, Departamento de Guatemala, Guatemala

Kowloon, Kowloon, Hong Kong

Wong Tai Sin, Kowloon, Hong Kong

Pok Fu Lam, Southern District, Hong Kong

Pécs, Baranya, Hungary

Gyula, Bekes County, Hungary

Miskolc, Borsod-Abauj Zemplen county, Hungary

Budapest, Budapest, Hungary

Kalocsa, Bács-Kiskun county, Hungary

Makó, Csongrád megye, Hungary

Szentes, Csongrád megye, Hungary

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Zalaegerszeg, Zala County, Hungary

Hyderabad, Andhra Pradesh, India

Patna, Bihar, India

Karnāl, Haryana, India

Bangalore, Karnataka, India

Belagavi, Karnataka, India

Bhopal, Madhya Pradesh, India

Mumbai, Maharashtra, India

Trichy, Tamil Nadu, India

Kfar Saba, Center District, Israel

Kfar Saba, Central District, Israel

Matan, Central District, Israel

Petah Tikva, Central District, Israel

Hadera, Haifa District, Israel

Haifa, Haifa District, Israel

Jerusalem, Jerusalem, Israel

Nahariya, Northern District, Israel

Safed, Northern District, Israel

Ashkelon, Southern District, Israel

Beersheba, Southern District, Israel

Holon, Tel Aviv, Israel

Tel Aviv, Tel Aviv, Israel

Safed, , Israel

Milan, Milan, Italy

Perugia, Perugia, Italy

Pistoia, Pistoia, Italy

Daugavpils, , Latvia

Liepāja, , Latvia

Limbaži, , Latvia

Ogre, , Latvia

Riga, , Latvia

Talsi, , Latvia

Tukums, , Latvia

Valmiera, , Latvia

Alytus, , Lithuania

Kaunas, , Lithuania

Kėdainiai, , Lithuania

Klaipėda, , Lithuania

Palanga, , Lithuania

Panevezys, , Lithuania

Vilnius, , Lithuania

Ipoh, , Malaysia

Kajang, , Malaysia

Kota Bharu, , Malaysia

Kuala Terengganu, , Malaysia

Kuantan, , Malaysia

Malacca, , Malaysia

Taiping, , Malaysia

Tlalnepantla, Edo de Mexico, Mexico

Guadalajara, Jalisco, Mexico

Mexico City, Mexico City, Mexico

Monterrey, Nuevo León, Mexico

Huixquilucan Edo. de Mexico, , Mexico

Mexico City, , Mexico

Auckland, , New Zealand

Christchurch, , New Zealand

Hamilton, , New Zealand

Otahuhu, , New Zealand

Palmerston North, , New Zealand

Takapuna, , New Zealand

Tauranga, , New Zealand

Wellington, , New Zealand

Chiclayo, Lambayeque, Peru

Lima, San Juan de Miraflores, Peru

Ica, , Peru

Manila, , Philippines

Bytom, , Poland

Gniewkowo, , Poland

Krakow, , Poland

Radom, , Poland

Rzeszów, , Poland

Tychy, , Poland

Warsaw, , Poland

Ponce, , Puerto Rico

San Juan, , Puerto Rico

Bacau, , Romania

Bucharest, , Romania

Galati, , Romania

Oradea, , Romania

Sibiu, , Romania

Târgu Mureş, , Romania

Arkhangelsk, , Russia

Irkutsk, , Russia

Moscow, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Smolensk, , Russia

Yaroslavl, , Russia

Singapore, , Singapore

Port Elizabeth, Eastern Cape, South Africa

Johannesburg, Gauteng, South Africa

Pretoria, Gauteng, South Africa

Durban, KwaZulu-Natal, South Africa

Tongaat, KwaZulu-Natal, South Africa

Cape Town, Western Cape, South Africa

Gwangju, Honam, South Korea

Daejeon, Hoseo, South Korea

Daegu, Yeongnam, South Korea

Barcelona, Catalonia, Spain

Santiago de Compostela, Galicia, Spain

Alicante, , Spain

Amphure Muang, , Thailand

Bangkok, , Thailand

Chiang Mai, , Thailand

Khon Kaen, , Thailand

Dnepropertovsk, , Ukraine

Dnipropetrovsk, , Ukraine

Donetsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Vinnytsa, , Ukraine

Vinnytsia, , Ukraine

Zaporizhye, , Ukraine

Zaporizhzhya, , Ukraine

Aintree-Liverpool, , United Kingdom

Bath, , United Kingdom

Bournemouth, , United Kingdom

Dundee, , United Kingdom

London, , United Kingdom

Stevenage, , United Kingdom

Swansea, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Brazil; Canada; Chile; Germany; Guatemala; Hong Kong; Hungary; India; Israel; Italy; Latvia; Lithuania; Malaysia; Mexico; New Zealand; Peru; Philippines; Poland; Puerto Rico; Romania; Russia; Singapore; South Africa; South Korea; Spain; Thailand; Ukraine; United Kingdom

References

Gordon J, McEwan P, Hurst M, Puelles J. The Cost-Effectiveness of Alogliptin Versus Sulfonylurea as Add-on Therapy to Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus. Diabetes Ther. 2016 Dec;7(4):825-845. doi: 10.1007/s13300-016-0206-7. Epub 2016 Oct 27.

Reference Type: DERIVED

PMID: 27787778 (View on PubMed)

Other Identifiers

2008-007444-34

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1111-7397

Identifier Type: REGISTRY

Identifier Source: secondary_id

HKCTR-862

Identifier Type: REGISTRY

Identifier Source: secondary_id

DOH-27-0709-2825

Identifier Type: REGISTRY

Identifier Source: secondary_id

09/H0703/66

Identifier Type: REGISTRY

Identifier Source: secondary_id

NMRR-09-203-3590

Identifier Type: REGISTRY

Identifier Source: secondary_id

SYR-322_305

Identifier Type: -

Identifier Source: org_study_id