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Efficacy and Safety of Alogliptin Plus Metformin in Patients With Type 2 Diabetes (AM7D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01023581
Recruitment Status : Completed
First Posted : December 2, 2009
Results First Posted : March 26, 2013
Last Update Posted : March 26, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Alogliptin Drug: Metformin Drug: Alogliptin Placebo Drug: Metformin Placebo Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 784 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Alogliptin Plus Metformin, Alogliptin Alone, or Metformin Alone in Subjects With Type 2 Diabetes
Study Start Date : November 2009
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Alogliptin placebo-matching tablets, orally, twice daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
Drug: Alogliptin Placebo
Alogliptin placebo-matching tablets.

Drug: Metformin Placebo
Metformin placebo-matching capsules.

Experimental: Alogliptin 25 QD
Alogliptin 25 mg, tablets, orally, once daily (QD) and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322

Drug: Metformin Placebo
Metformin placebo-matching capsules.

Experimental: 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.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322

Drug: Metformin Placebo
Metformin placebo-matching capsules.

Active Comparator: Metformin 500 BID
Alogliptin placebo-matching tablets, orally, twice daily and Metformin 500 mg capsules, orally, twice daily for up to 26 weeks.
Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin

Drug: Alogliptin Placebo
Alogliptin placebo-matching tablets.

Active Comparator: Metformin 1000 BID
Alogliptin placebo-matching tablets, orally, twice daily and Metformin 1000 mg capsules, orally, twice daily for up to 26 weeks.
Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin

Drug: Alogliptin Placebo
Alogliptin placebo-matching tablets.

Experimental: 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.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322

Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin

Experimental: 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.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322

Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin




Primary Outcome Measures :
  1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 [ Time Frame: Baseline and Week 26. ]
    The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).


Secondary Outcome Measures :
  1. Change From Baseline in HbA1c Over Time [ Time Frame: Baseline and Weeks 4, 8, 12, 16, and 20. ]

    The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was assessed at Weeks 4, 8, 12, 16 and 20.

    Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as fixed effects, and baseline HbA1c as a covariate.


  2. Change From Baseline in Fasting Plasma Glucose Over Time [ Time Frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26. ]
    The change from Baseline in fasting plasma glucose was assessed at Weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as fixed effects, and baseline fasting plasma glucose as a covariate.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01023581


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Locations
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United States, Alabama
Dothan, Alabama, United States
Muscle Shoals, Alabama, United States
Pell City, Alabama, United States
United States, Arizona
Chandler, Arizona, United States
Mesa, Arizona, United States
Phoenix, Arizona, United States
Sierra Vista, Arizona, United States
Tempe, Arizona, United States
United States, Arkansas
Little Rock, Arkansas, United States
Searcy, Arkansas, United States
Tempe, Arkansas, United States
United States, California
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
United States, Colorado
Colorado Springs, Colorado, United States
United States, Florida
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
United States, Georgia
Atlanta, Georgia, United States
Blue Ridge, Georgia, United States
Decatur, Georgia, United States
Lawrenceville, Georgia, United States
United States, Idaho
Hayden Lake, Idaho, United States
United States, Illinois
Chicago, Illinois, United States
Melrose Park, Illinois, United States
United States, Indiana
La Porte, Indiana, United States
Mishawaka, Indiana, United States
United States, Iowa
Council Bluffs, Iowa, United States
Dubuque, Iowa, United States
United States, Kansas
Topeka, Kansas, United States
United States, Kentucky
Lexington, Kentucky, United States
Louisville, Kentucky, United States
United States, Louisiana
Marrero, Louisiana, United States
United States, Maryland
Oxon Hill, Maryland, United States
United States, Massachusetts
North Dartmouth, Massachusetts, United States
United States, Michigan
Dearborn, Michigan, United States
Flint, Michigan, United States
Kalamazoo, Michigan, United States
United States, Mississippi
Picayune, Mississippi, United States
United States, Missouri
St. Louis, Missouri, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, Nevada
Henderson, Nevada, United States
Las Vegas, Nevada, United States
United States, New Jersey
Brick, New Jersey, United States
Elizabeth, New Jersey, United States
United States, New York
North Massapequa, New York, United States
United States, North Carolina
Asheville, North Carolina, United States
Charlotte, North Carolina, United States
Greensboro, North Carolina, United States
Mooresville, North Carolina, United States
United States, North Dakota
Fargo, North Dakota, United States
United States, Ohio
Cincinnati, Ohio, United States
Cleveland, Ohio, United States
Gallipolis, Ohio, United States
Mason, Ohio, United States
Maumee, Ohio, United States
United States, Oklahoma
Norman, Oklahoma, United States
Oklahoma City, Oklahoma, United States
Tulsa, Oklahoma, United States
United States, Pennsylvania
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
United States, South Carolina
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
United States, Tennessee
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
United States, Texas
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
United States, Utah
Bountiful, Utah, United States
Ogden, Utah, United States
Salt Lake City, Utah, United States
United States, Vermont
South Burlington, Vermont, United States
United States, Virginia
Petersburg, Virginia, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Czech Republic
Hradec Kralove, Czech Republic
Olomouc, Czech Republic
Ostrava, Czech Republic
Praha 10, Czech Republic
Zlin, Czech Republic
Znojmo, Czech Republic
Hungary
Budaors, Hungary
Debrecen, Hungary
Gyongyos, Hungary
Gyor, Hungary
Gyula, Hungary
Komarom, Hungary
Szolnok, Hungary
Zalaegerszeg, Hungary
Israel
Haifa, Israel
Holon, Israel
Kfar Saba, Israel
Nahariya, Israel
Safed, Israel
Lithuania
Kaunas, Lithuania
Kedainiai, Lithuania
Klaipeda, Lithuania
Vilnius, Lithuania
Mexico
Acapulco, Guerrero, Mexico
Cuernavaca, Mexico
Culiacan, Sinoloa, Mexico
Distrito Federal, Mexico
Durango, Durango, Mexico
Durango, Mexico
Guadalajara, Mexico
Mexico City, Mexico, Mexico
Mexico City, Mexico
Mexico, DF, Mexico
Monclova, Coahuila, Mexico
Monterrey, NL, Mexico
Monterrey, Mexico
Pachuca, Hidalgo, Mexico
Pachuca, Mexico
Saltillo, Mexico
Tijuana, Baja California, Mexico
Zapopan, Jalisco, Mexico
Poland
Bialystok, Poland
Bytom, Poland
Gniewkowo, Poland
Grodzisk Mazowiecki, Poland
Kamieniec Zabkowicki, Poland
Leczyca, Poland
Warszawa, Poland
Wroclaw, Poland
Puerto Rico
Caguas, Puerto Rico
Cidra, Puerto Rico
Ponce, Puerto Rico
Salinas, Puerto Rico
San Juan, Puerto Rico
Santurce, Puerto Rico
Trujilo Alto, Puerto Rico
Romania
Bacau, Romania
Baia Mare, Romania
Bucharest, Romania
Constanta, Romania
Iasi, Romania
Ploiesti, Romania
Russian Federation
Arkhangelsk, Russian Federation
Irkutsk, Russian Federation
Kemerovo, Russian Federation
Moscow, Russian Federation
Perm, Russian Federation
St. Petersburg, Russian Federation
Ufa, Russian Federation
Slovakia
Banska Bystrica, Slovakia
Kosice, Slovakia
Lucenec, Slovakia
Nitra, Slovakia
Presov, Slovakia
Prievidza, Slovakia
Sahy, Slovakia
Zilina, Slovakia
South Africa
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
Ukraine
Dnipropetrovsk, Ukraine
Donetsk, Ukraine
Ivano-Frankivsk, Ukraine
Kharkiv, Ukraine
Kyiv, Ukraine
Lviv, Ukraine
Odesa, Ukraine
Vinnytsya, Ukraine
Zaporizhzhya, Ukraine
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Vice President, Clinical Science Takeda

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01023581     History of Changes
Other Study ID Numbers: SYR-322MET_302
2009-012652-24 ( Registry Identifier: EudraCT )
U1111-1112-1912 ( Registry Identifier: WHO )
DOH-27-0910-3155 ( Registry Identifier: SANCTR )
CTRI/2010/091/000253 ( Registry Identifier: CTRI )
First Posted: December 2, 2009    Key Record Dates
Results First Posted: March 26, 2013
Last Update Posted: March 26, 2013
Last Verified: February 2013

Keywords provided by Takeda:
Type 2 Diabetes mellitus
Non-insulin dependent diabetes mellitus
Drug Therapy
Hypoglycemia,
Hyperglycemia

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Alogliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action