Efficacy and Safety of Alogliptin Plus Metformin in Patients With Type 2 Diabetes
Overview[ - collapse ][ - ]
| Purpose | 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 | Diabetes Mellitus, Type 2 |
| Intervention | Drug: Alogliptin Drug: Metformin Drug: Alogliptin Placebo Drug: Metformin Placebo |
| Phase | Phase 3 |
| Sponsor | Takeda |
| Responsible Party | Takeda |
| ClinicalTrials.gov Identifier | NCT01023581 |
| First Received | December 1, 2009 |
| Last Updated | February 17, 2013 |
| Last verified | February 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | December 1, 2009 |
|---|---|
| Last Updated Date | February 17, 2013 |
| Start Date | November 2009 |
| Estimated Primary Completion Date | June 2011 |
| Current Primary Outcome Measures | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 [Time Frame: Baseline and Week 26.] [Designated as safety issue: No]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). |
| Current Secondary Outcome Measures |
|
Descriptive Information[ + expand ][ + ]
| Brief Title | Efficacy and Safety of Alogliptin Plus Metformin in Patients With Type 2 Diabetes |
|---|---|
| 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 |
| 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. |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition | Diabetes Mellitus, Type 2 |
| Intervention | Drug: Alogliptin Alogliptin tablets. Other Names: SYR-322Drug: Metformin Metformin capsules Other Names:
Alogliptin placebo-matching tablets. Drug: Metformin Placebo Metformin placebo-matching capsules. |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 784 |
| Estimated Completion Date | June 2011 |
| Estimated Primary Completion Date | June 2011 |
| 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. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Czech Republic, Hungary, Israel, Lithuania, Mexico, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, South Africa, Ukraine |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01023581 |
|---|---|
| Other Study ID Numbers | SYR-322MET_302 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Takeda |
| Study Sponsor | Takeda |
| Collaborators | Not Provided |
| Investigators | Study Director: Vice President, Clinical Science Takeda |
| Verification Date | February 2013 |
Locations[ + expand ][ + ]
| United States, Alabama | Dothan, Alabama, United States |
|---|---|
| United States, Alabama | Muscle Shoals, Alabama, United States |
| United States, Alabama | Pell City, Alabama, United States |
| United States, Arizona | Chandler, Arizona, United States |
| United States, Arizona | Mesa, Arizona, United States |
| United States, Arizona | Phoenix, Arizona, United States |
| United States, Arizona | Sierra Vista, Arizona, United States |
| United States, Arizona | Tempe, Arizona, United States |
| United States, Arkansas | Little Rock, Arkansas, United States |
| United States, Arkansas | Searcy, Arkansas, United States |
| United States, Arkansas | Tempe, Arkansas, United States |
| United States, California | Anaheim, California, United States |
| United States, California | Buena Park, California, United States |
| United States, California | Cathedral City, California, United States |
| United States, California | National City, California, United States |
| United States, California | Pismo Beach, California, United States |
| United States, California | Roseville, California, United States |
| United States, California | Santa Ana, California, United States |
| United States, Colorado | Colorado Springs, Colorado, United States |
| United States, Florida | Boca Raton, Florida, United States |
| United States, Florida | Bradenton, Florida, United States |
| United States, Florida | Cutler Bay, Florida, United States |
| United States, Florida | Hialeah, Florida, United States |
| United States, Florida | Lauderdale Lakes, Florida, United States |
| United States, Florida | Miami, Florida, United States |
| United States, Florida | Ocala, Florida, United States |
| United States, Florida | Opa Locka, Florida, United States |
| United States, Florida | Orlando, Florida, United States |
| United States, Florida | Panama City, Florida, United States |
| United States, Florida | Pembroke Pines, Florida, United States |
| United States, Georgia | Atlanta, Georgia, United States |
| United States, Georgia | Blue Ridge, Georgia, United States |
| United States, Georgia | Decatur, Georgia, United States |
| United States, Georgia | Lawrenceville, Georgia, United States |
| United States, Idaho | Hayden Lake, Idaho, United States |
| United States, Illinois | Chicago, Illinois, United States |
| United States, Illinois | Melrose Park, Illinois, United States |
| United States, Indiana | La Porte, Indiana, United States |
| United States, Indiana | Mishawaka, Indiana, United States |
| United States, Iowa | Council Bluffs, Iowa, United States |
| United States, Iowa | Dubuque, Iowa, United States |
| United States, Kansas | Topeka, Kansas, United States |
| United States, Kentucky | Lexington, Kentucky, United States |
| United States, Kentucky | 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 |
| United States, Michigan | Flint, Michigan, United States |
| United States, Michigan | 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 |
| United States, Nevada | Las Vegas, Nevada, United States |
| United States, New Jersey | Brick, New Jersey, United States |
| United States, New Jersey | Elizabeth, New Jersey, United States |
| United States, New York | North Massapequa, New York, United States |
| United States, North Carolina | Asheville, North Carolina, United States |
| United States, North Carolina | Charlotte, North Carolina, United States |
| United States, North Carolina | Greensboro, North Carolina, United States |
| United States, North Carolina | Mooresville, North Carolina, United States |
| United States, North Dakota | Fargo, North Dakota, United States |
| United States, Ohio | Cincinnati, Ohio, United States |
| United States, Ohio | Cleveland, Ohio, United States |
| United States, Ohio | Gallipolis, Ohio, United States |
| United States, Ohio | Mason, Ohio, United States |
| United States, Ohio | Maumee, Ohio, United States |
| United States, Oklahoma | Norman, Oklahoma, United States |
| United States, Oklahoma | Oklahoma City, Oklahoma, United States |
| United States, Oklahoma | Tulsa, Oklahoma, United States |
| United States, Pennsylvania | Altoona, Pennsylvania, United States |
| United States, Pennsylvania | Bensalem, Pennsylvania, United States |
| United States, Pennsylvania | Downingtown, Pennsylvania, United States |
| United States, Pennsylvania | Fleetwood, Pennsylvania, United States |
| United States, Pennsylvania | Perkasie, Pennsylvania, United States |
| United States, Pennsylvania | Shippensburg, Pennsylvania, United States |
| United States, Pennsylvania | Tipton, Pennsylvania, United States |
| United States, Pennsylvania | Uniontown, Pennsylvania, United States |
| United States, South Carolina | Columbia, South Carolina, United States |
| United States, South Carolina | Greenville, South Carolina, United States |
| United States, South Carolina | Murrells Inlet, South Carolina, United States |
| United States, South Carolina | North Myrtle Beach, South Carolina, United States |
| United States, South Carolina | Taylors, South Carolina, United States |
| United States, Tennessee | Brentwood, Tennessee, United States |
| United States, Tennessee | Bristol, Tennessee, United States |
| United States, Tennessee | Crossville, Tennessee, United States |
| United States, Tennessee | Johnson City, Tennessee, United States |
| United States, Tennessee | McKenzie, Tennessee, United States |
| United States, Tennessee | Spring Hill, Tennessee, United States |
| United States, Texas | Carrollton, Texas, United States |
| United States, Texas | Dallas, Texas, United States |
| United States, Texas | Deer Park, Texas, United States |
| United States, Texas | El Paso, Texas, United States |
| United States, Texas | Houston, Texas, United States |
| United States, Texas | Hurst, Texas, United States |
| United States, Texas | Katy, Texas, United States |
| United States, Texas | Odessa, Texas, United States |
| United States, Texas | San Antonio, Texas, United States |
| United States, Texas | Schertz, Texas, United States |
| United States, Texas | Spring, Texas, United States |
| United States, Texas | Sugarland, Texas, United States |
| United States, Texas | Temple, Texas, United States |
| United States, Utah | Bountiful, Utah, United States |
| United States, Utah | Ogden, Utah, United States |
| United States, Utah | 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 |
| Czech Republic | Olomouc, Czech Republic |
| Czech Republic | Ostrava, Czech Republic |
| Czech Republic | Praha 10, Czech Republic |
| Czech Republic | Zlin, Czech Republic |
| Czech Republic | Znojmo, Czech Republic |
| Hungary | Budaors, Hungary |
| Hungary | Debrecen, Hungary |
| Hungary | Gyongyos, Hungary |
| Hungary | Gyor, Hungary |
| Hungary | Gyula, Hungary |
| Hungary | Komarom, Hungary |
| Hungary | Szolnok, Hungary |
| Hungary | Zalaegerszeg, Hungary |
| Israel | Haifa, Israel |
| Israel | Holon, Israel |
| Israel | Kfar Saba, Israel |
| Israel | Nahariya, Israel |
| Israel | Safed, Israel |
| Lithuania | Kaunas, Lithuania |
| Lithuania | Kedainiai, Lithuania |
| Lithuania | Klaipeda, Lithuania |
| Lithuania | Vilnius, Lithuania |
| Mexico | Acapulco, Guerrero, Mexico |
| Mexico | Cuernavaca, Mexico |
| Mexico | Culiacan, Sinoloa, Mexico |
| Mexico | Distrito Federal, Mexico |
| Mexico | Durango, Mexico |
| Mexico | Durango, Durango, Mexico |
| Mexico | Guadalajara, Mexico |
| Mexico | Mexico City, Mexico |
| Mexico | Mexico City, Mexico, Mexico |
| Mexico | Mexico, DF, Mexico |
| Mexico | Monclova, Coahuila, Mexico |
| Mexico | Monterrey, Mexico |
| Mexico | Monterrey, NL, Mexico |
| Mexico | Pachuca, Mexico |
| Mexico | Pachuca, Hidalgo, Mexico |
| Mexico | Saltillo, Mexico |
| Mexico | Tijuana, Baja California, Mexico |
| Mexico | Zapopan, Jalisco, Mexico |
| Poland | Bialystok, Poland |
| Poland | Bytom, Poland |
| Poland | Gniewkowo, Poland |
| Poland | Grodzisk Mazowiecki, Poland |
| Poland | Kamieniec Zabkowicki, Poland |
| Poland | Leczyca, Poland |
| Poland | Warszawa, Poland |
| Poland | Wroclaw, Poland |
| Puerto Rico | Caguas, Puerto Rico |
| Puerto Rico | Cidra, Puerto Rico |
| Puerto Rico | Ponce, Puerto Rico |
| Puerto Rico | Salinas, Puerto Rico |
| Puerto Rico | San Juan, Puerto Rico |
| Puerto Rico | Santurce, Puerto Rico |
| Puerto Rico | Trujilo Alto, Puerto Rico |
| Romania | Bacau, Romania |
| Romania | Baia Mare, Romania |
| Romania | Bucharest, Romania |
| Romania | Constanta, Romania |
| Romania | Iasi, Romania |
| Romania | Ploiesti, Romania |
| Russian Federation | Arkhangelsk, Russian Federation |
| Russian Federation | Irkutsk, Russian Federation |
| Russian Federation | Kemerovo, Russian Federation |
| Russian Federation | Moscow, Russian Federation |
| Russian Federation | Perm, Russian Federation |
| Russian Federation | St. Petersburg, Russian Federation |
| Russian Federation | Ufa, Russian Federation |
| Slovakia | Banska Bystrica, Slovakia |
| Slovakia | Kosice, Slovakia |
| Slovakia | Lucenec, Slovakia |
| Slovakia | Nitra, Slovakia |
| Slovakia | Presov, Slovakia |
| Slovakia | Prievidza, Slovakia |
| Slovakia | Sahy, Slovakia |
| Slovakia | Zilina, Slovakia |
| South Africa, Gauteng | Centurion, Gauteng, South Africa |
| South Africa, Gauteng | Johannesburg, Gauteng, South Africa |
| South Africa, Gauteng | Pretoria, Gauteng, South Africa |
| South Africa, Kwazulu-Natal | Durban, Kwazulu-Natal, South Africa |
| South Africa, Western Cape | Cape Town, Western Cape, South Africa |
| South Africa | Pretoria, South Africa |
| Ukraine | Dnipropetrovsk, Ukraine |
| Ukraine | Donetsk, Ukraine |
| Ukraine | Ivano-Frankivsk, Ukraine |
| Ukraine | Kharkiv, Ukraine |
| Ukraine | Kyiv, Ukraine |
| Ukraine | Lviv, Ukraine |
| Ukraine | Odesa, Ukraine |
| Ukraine | Vinnytsya, Ukraine |
| Ukraine | Zaporizhzhya, Ukraine |