Efficacy and Safety of Alogliptin Plus Metformin in Patients With Type 2 Diabetes

NCT ID: NCT01023581

Last Updated: 2013-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 784 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2011-06-30

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of alogliptin combined with metformin, once daily (QD) or twice daily (BID), in participants with Type 2 Diabetes.

Detailed Description

There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% are type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected.

Metformin is the usual choice of first-line therapy for type 2 diabetes. Metformin targets insulin resistance in type 2 diabetes by inhibiting hepatic glucose production and stimulating glucose uptake in skeletal muscle and adipose tissue, which results in a long-term glucose-lowering effect.

Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes.

Based on the potential, complimentary mechanisms of action of alogliptin and metformin, this study will compare the safety and efficacy of alogliptin and metformin (SYR-322MET) on improving glycemic control in patients with type 2 diabetes mellitus who are inadequately controlled by diet adjustment and exercise alone.

Participants taking part in this study will receive dietary and exercise coaching, and will monitor their own blood glucose concentrations with a home glucose monitor. Participants will also be required to maintain a hypoglycemic diary throughout the course of the study. Participation in this study is expected to last up to 34 weeks.

Conditions

Diabetes Mellitus, Type 2

Study Design

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

Study Groups

Placebo

Alogliptin placebo-matching tablets, orally, twice daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.

Group Type: PLACEBO_COMPARATOR

Alogliptin Placebo

Intervention Type: DRUG

Alogliptin placebo-matching tablets.

Metformin Placebo

Intervention Type: DRUG

Metformin placebo-matching capsules.

Alogliptin 25 QD

Alogliptin 25 mg, tablets, orally, once daily (QD) and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin tablets.

Metformin Placebo

Intervention Type: DRUG

Metformin placebo-matching capsules.

Alogliptin 12.5 BID

Alogliptin 12.5 mg, tablets, orally, twice daily (BID) and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin tablets.

Metformin Placebo

Intervention Type: DRUG

Metformin placebo-matching capsules.

Metformin 500 BID

Alogliptin placebo-matching tablets, orally, twice daily and Metformin 500 mg capsules, orally, twice daily for up to 26 weeks.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin capsules

Alogliptin Placebo

Intervention Type: DRUG

Alogliptin placebo-matching tablets.

Metformin 1000 BID

Alogliptin placebo-matching tablets, orally, twice daily and Metformin 1000 mg capsules, orally, twice daily for up to 26 weeks.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin capsules

Alogliptin Placebo

Intervention Type: DRUG

Alogliptin placebo-matching tablets.

Alogliptin 12.5 BID + Metformin 500 BID

Alogliptin 12.5mg, tablets, orally, twice daily and Metformin 500 mg, capsules, orally, twice daily for up to 26 weeks.

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin tablets.

Metformin

Intervention Type: DRUG

Metformin capsules

Alogliptin 12.5 BID + Metformin 1000 BID

Alogliptin 12.5 mg, tablets, orally, twice daily and Metformin 1000 mg, capsules, orally, twice daily for up to 26 weeks.

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin tablets.

Metformin

Intervention Type: DRUG

Metformin capsules

Interventions

Alogliptin

Alogliptin tablets.

Intervention Type: DRUG

Metformin

Metformin capsules

Intervention Type: DRUG

Alogliptin Placebo

Alogliptin placebo-matching tablets.

Intervention Type: DRUG

Metformin Placebo

Metformin placebo-matching capsules.

Intervention Type: DRUG

Other Intervention Names

SYR-322; Glucophage; Glucophage XR; Riomet; Fortamet; Glumetza; Obimet; Dianben; Diabex; Diaformin

Eligibility Criteria

Inclusion Criteria

• Has historical diagnosis of Type 2 Diabetes Mellitus.
• Has been treated with diet and exercise for at least 2 months prior to Screening, and has a Glycosylated Hemoglobin concentration between 7.5% and 10.0%, inclusive at Screening.
• Has received less than 7 days of any antidiabetic medication within 2 months prior to Screening.
• Body mass index greater than or equal to 23 kg/m^2 and less than or equal to 45 kg/m^2 (except for Asian or Asian-descendant subjects for whom the range is between 20 and 35 kg/ m^2, inclusive).
• Fasting C-peptide concentration greater than or equal to 0.8 ng/mL.
• Regularly using other, non-excluded, medications must be on a stable dose for at least the 4 weeks prior to Screening.
• Females of childbearing potential and males who are sexually active agree to routinely use adequate contraception from Screening throughout the duration of the study.
• Able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete patient diaries.

Exclusion Criteria

• Hemoglobin less than 12 g/dL for males and less than 10 g/dL for females at Screening Visit.
• Has a history of any hemoglobinopathy that may affect determination of Glycosylated Hemoglobin.
• Has a history of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
• Has a history of treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery.
• Has a history of diabetic ketoacidosis or hyperosmolar non-ketotic coma.
• Has systolic blood pressure greater than or equal to 150 mmHg and /or diastolic pressure greater than or equal to 90 mmHg at Screening visit.
• Has New York Heart Association Class III to IV heart failure.
• Has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 90 days prior to Screening.
• Has Alanine aminotransferase greater than 3 times the upper limit of normal at Screening.
• Has a history of alcohol or substance abuse with the 2 years prior to Screening.
• Serum creatinine greater than or equal to 1.5 mg/dL for males and greater than or equal to 1.4 mg/dL for females.
• Has history of cancer, other than squamous cell or basal cell carcinoma of the skin that has not been in full remission for at least 5 years prior to Screening.
• Has a history of infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
• Has any major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
• Has received any investigational drug within the 90 days prior to Screening.
• Has a history of hypersensitivity or allergy to alogliptin, other DPP-4 inhibitors, metformin or related compounds.
• Has used oral or systematically injected glucocorticoids or weight loss drugs prior to 2 months to screening.

• 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

Vice President, Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Dothan, Alabama, United States

Muscle Shoals, Alabama, United States

Pell City, Alabama, United States

Chandler, Arizona, United States

Mesa, Arizona, United States

Phoenix, Arizona, United States

Sierra Vista, Arizona, United States

Tempe, Arizona, United States

Little Rock, Arkansas, United States

Searcy, Arkansas, United States

Tempe, Arkansas, United States

Anaheim, California, United States

Buena Park, California, United States

Cathedral City, California, United States

National City, California, United States

Pismo Beach, California, United States

Roseville, California, United States

Santa Ana, California, United States

Colorado Springs, Colorado, United States

Boca Raton, Florida, United States

Bradenton, Florida, United States

Cutler Bay, Florida, United States

Hialeah, Florida, United States

Lauderdale Lakes, Florida, United States

Miami, Florida, United States

Ocala, Florida, United States

Opa-locka, Florida, United States

Orlando, Florida, United States

Panama City, Florida, United States

Pembroke Pines, Florida, United States

Atlanta, Georgia, United States

Blue Ridge, Georgia, United States

Decatur, Georgia, United States

Lawrenceville, Georgia, United States

Hayden Lake, Idaho, United States

Chicago, Illinois, United States

Melrose Park, Illinois, United States

La Porte, Indiana, United States

Mishawaka, Indiana, United States

Council Bluffs, Iowa, United States

Dubuque, Iowa, United States

Topeka, Kansas, United States

Lexington, Kentucky, United States

Louisville, Kentucky, United States

Marrero, Louisiana, United States

Oxon Hill, Maryland, United States

North Dartmouth, Massachusetts, United States

Dearborn, Michigan, United States

Flint, Michigan, United States

Kalamazoo, Michigan, United States

Picayune, Mississippi, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Henderson, Nevada, United States

Las Vegas, Nevada, United States

Brick, New Jersey, United States

Elizabeth, New Jersey, United States

North Massapequa, New York, United States

Asheville, North Carolina, United States

Charlotte, North Carolina, United States

Greensboro, North Carolina, United States

Mooresville, North Carolina, United States

Fargo, North Dakota, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Gallipolis, Ohio, United States

Mason, Ohio, United States

Maumee, Ohio, United States

Norman, Oklahoma, United States

Oklahoma City, Oklahoma, United States

Tulsa, Oklahoma, United States

Altoona, Pennsylvania, United States

Bensalem, Pennsylvania, United States

Downingtown, Pennsylvania, United States

Fleetwood, Pennsylvania, United States

Perkasie, Pennsylvania, United States

Shippensburg, Pennsylvania, United States

Tipton, Pennsylvania, United States

Uniontown, Pennsylvania, United States

Columbia, South Carolina, United States

Greenville, South Carolina, United States

Murrells Inlet, South Carolina, United States

North Myrtle Beach, South Carolina, United States

Taylors, South Carolina, United States

Brentwood, Tennessee, United States

Bristol, Tennessee, United States

Crossville, Tennessee, United States

Johnson City, Tennessee, United States

McKenzie, Tennessee, United States

Spring Hill, Tennessee, United States

Carrollton, Texas, United States

Dallas, Texas, United States

Deer Park, Texas, United States

El Paso, Texas, United States

Houston, Texas, United States

Hurst, Texas, United States

Katy, Texas, United States

Odessa, Texas, United States

San Antonio, Texas, United States

Schertz, Texas, United States

Spring, Texas, United States

Sugarland, Texas, United States

Temple, Texas, United States

Bountiful, Utah, United States

Ogden, Utah, United States

Salt Lake City, Utah, United States

South Burlington, Vermont, United States

Petersburg, Virginia, United States

Milwaukee, Wisconsin, United States

Hradec Králové, , Czechia

Olomouc, , Czechia

Ostrava, , Czechia

Prague, , Czechia

Zlín, , Czechia

Znojmo, , Czechia

Budaörs, , Hungary

Debrecen, , Hungary

Gyöngyös, , Hungary

Győr, , Hungary

Gyula, , Hungary

Komárom, , Hungary

Szolnok, , Hungary

Zalaegerszeg, , Hungary

Haifa, , Israel

Holon, , Israel

Kfar Saba, , Israel

Nahariya, , Israel

Safed, , Israel

Kaunas, , Lithuania

Kėdainiai, , Lithuania

Klaipėda, , Lithuania

Vilnius, , Lithuania

Acapulco, Guerrero, , Mexico

Cuernavaca, , Mexico

Culiacan, Sinoloa, , Mexico

Distrito Federal, , Mexico

Durango, , Mexico

Durango, Durango, , Mexico

Guadalajara, , Mexico

Mexico City, , Mexico

Mexico City, Mexico, , Mexico

Monclova, Coahuila, , Mexico

Monterrey, , Mexico

Monterrey, NL, , Mexico

Pachuca, , Mexico

Pachuca, Hidalgo, , Mexico

Saltillo, , Mexico

Tijuana, Baja California, , Mexico

Zapopan, Jalisco, , Mexico

Bialystok, , Poland

Bytom, , Poland

Gniewkowo, , Poland

Grodzisk Mazowiecki, , Poland

Kamieniec Ząbkowicki, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Łęczyca, , Poland

Caguas, PR, Puerto Rico

Cidra, PR, Puerto Rico

Ponce, PR, Puerto Rico

Salinas, PR, Puerto Rico

San Juan, PR, Puerto Rico

Santurce, PR, Puerto Rico

San Juan, , Puerto Rico

Trujilo Alto, , Puerto Rico

Bacau, , Romania

Baia Mare, , Romania

Bucharest, , Romania

Constanța, , Romania

Iași, , Romania

Ploieşti, , Romania

Arkhangelsk, , Russia

Irkutsk, , Russia

Kemerovo, , Russia

Moscow, , Russia

Perm, , Russia

Saint Petersburg, , Russia

Ufa, , Russia

Banská Bystrica, , Slovakia

Košice, , Slovakia

Lučenec, , Slovakia

Nitra, , Slovakia

Prešov, , Slovakia

Prievidza, , Slovakia

Šahy, , Slovakia

Žilina, , Slovakia

Centurion, Gauteng, South Africa

Johannesburg, Gauteng, South Africa

Pretoria, Gauteng, South Africa

Durban, KwaZulu-Natal, South Africa

Cape Town, Western Cape, South Africa

Pretoria, , South Africa

Dnipropetrovsk, , Ukraine

Donetsk, , Ukraine

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Odesa, , Ukraine

Vinnytsia, , Ukraine

Zaporizhzhya, , Ukraine

Countries

United States; Czechia; Hungary; Israel; Lithuania; Mexico; Poland; Puerto Rico; Romania; Russia; Slovakia; South Africa; Ukraine

References

Pratley RE, Fleck P, Wilson C. Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naive patients with type 2 diabetes: a randomized, double-blind, 6-month study. Diabetes Obes Metab. 2014 Jul;16(7):613-21. doi: 10.1111/dom.12258. Epub 2014 Feb 12.

Reference Type: DERIVED

PMID: 24400655 (View on PubMed)

Other Identifiers

2009-012652-24

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1112-1912

Identifier Type: REGISTRY

Identifier Source: secondary_id

DOH-27-0910-3155

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTRI/2010/091/000253

Identifier Type: REGISTRY

Identifier Source: secondary_id

SYR-322MET_302

Identifier Type: -

Identifier Source: org_study_id