Clinical trial NCT01023581: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Type 2 Diabetes mellitus
Non-insulin dependent diabetes mellitus
Drug Therapy
Hypoglycemia,
Hyperglycemia
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-12-02
Enrollment: 784
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
timeFrame: Baseline and Week 26.
Secondary outcomes:
measure: Change From Baseline in HbA1c Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, and 20.
measure: Change From Baseline in Fasting Plasma Glucose Over Time
timeFrame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Other outcomes:
Locations:
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country: United States
state: Alabama
city: Muscle Shoals
country: United States
state: Alabama
city: Pell City
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state: Alabama
city: Chandler
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state: Arizona
city: Mesa
country: United States
state: Arizona
city: Phoenix
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state: Arizona
city: Sierra Vista
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state: Arizona
city: Tempe
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state: Arizona
city: Little Rock
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state: Arkansas
city: Searcy
country: United States
state: Arkansas
city: Tempe
country: United States
state: Arkansas
city: Anaheim
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state: California
city: Buena Park
country: United States
state: California
city: Cathedral City
country: United States
state: California
city: National City
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state: California
city: Pismo Beach
country: United States
state: California
city: Roseville
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state: California
city: Santa Ana
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Boca Raton
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state: Florida
city: Bradenton
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state: Florida
city: Cutler Bay
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state: Florida
city: Hialeah
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state: Florida
city: Lauderdale Lakes
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state: Florida
city: Miami
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city: Ocala
country: United States
state: Florida
city: Opa Locka
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state: Florida
city: Orlando
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city: Panama City
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city: Pembroke Pines
country: United States
state: Florida
city: Atlanta
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state: Georgia
city: Blue Ridge
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state: Georgia
city: Decatur
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state: Georgia
city: Lawrenceville
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city: Hayden Lake
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state: Idaho
city: Chicago
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state: Illinois
city: Melrose Park
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state: Illinois
city: La Porte
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state: Indiana
city: Mishawaka
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city: Council Bluffs
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city: Louisville
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city: Marrero
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state: Louisiana
city: Oxon Hill
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state: Maryland
city: North Dartmouth
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state: Massachusetts
city: Dearborn
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state: Michigan
city: Flint
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city: Kalamazoo
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state: Mississippi
city: St. Louis
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city: Las Vegas
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city: Elizabeth
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city: Tulsa
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state: Pennsylvania
city: Bensalem
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city: Downingtown
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city: Fleetwood
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city: Perkasie
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city: Shippensburg
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state: Pennsylvania
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state: Pennsylvania
city: Columbia
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city: Greenville
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state: South Carolina
city: Murrells Inlet
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state: South Carolina
city: North Myrtle Beach
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state: South Carolina
city: Taylors
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state: South Carolina
city: Brentwood
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state: Tennessee
city: Bristol
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state: Tennessee
city: Crossville
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state: Tennessee
city: Johnson City
country: United States
state: Tennessee
city: McKenzie
country: United States
state: Tennessee
city: Spring Hill
country: United States
state: Tennessee
city: Carrollton
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Deer Park
country: United States
state: Texas
city: El Paso
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state: Texas
city: Houston
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state: Texas
city: Hurst
country: United States
state: Texas
city: Katy
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state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
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state: Texas
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state: Texas
city: Spring
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city: Sugarland
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state: Texas
city: Temple
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state: Texas
city: Bountiful
country: United States
state: Utah
city: Ogden
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city: Salt Lake City
country: United States
state: Utah
city: South Burlington
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state: Vermont
city: Petersburg
country: United States
state: Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Hradec Kralove
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Praha 10
country: Czech Republic
city: Zlin
country: Czech Republic
city: Znojmo
country: Czech Republic
city: Budaors
country: Hungary
city: Debrecen
country: Hungary
city: Gyongyos
country: Hungary
city: Gyor
country: Hungary
city: Gyula
country: Hungary
city: Komarom
country: Hungary
city: Szolnok
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Haifa
country: Israel
city: Holon
country: Israel
city: Kfar Saba
country: Israel
city: Nahariya
country: Israel
city: Safed
country: Israel
city: Kaunas
country: Lithuania
city: Kedainiai
country: Lithuania
city: Klaipeda
country: Lithuania
city: Vilnius
country: Lithuania
city: Acapulco, Guerrero
country: Mexico
city: Cuernavaca
country: Mexico
city: Culiacan, Sinoloa
country: Mexico
city: Distrito Federal
country: Mexico
city: Durango, Durango
country: Mexico
city: Durango
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico City, Mexico
country: Mexico
city: Mexico City
country: Mexico
city: Mexico, DF
country: Mexico
city: Monclova, Coahuila
country: Mexico
city: Monterrey, NL
country: Mexico
city: Monterrey
country: Mexico
city: Pachuca, Hidalgo
country: Mexico
city: Pachuca
country: Mexico
city: Saltillo
country: Mexico
city: Tijuana, Baja California
country: Mexico
city: Zapopan, Jalisco
country: Mexico
city: Bialystok
country: Poland
city: Bytom
country: Poland
city: Gniewkowo
country: Poland
city: Grodzisk Mazowiecki
country: Poland
city: Kamieniec Zabkowicki
country: Poland
city: Leczyca
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Caguas
country: Puerto Rico
city: Cidra
country: Puerto Rico
city: Ponce
country: Puerto Rico
city: Salinas
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Santurce
country: Puerto Rico
city: Trujilo Alto
country: Puerto Rico
city: Bacau
country: Romania
city: Baia Mare
country: Romania
city: Bucharest
country: Romania
city: Constanta
country: Romania
city: Iasi
country: Romania
city: Ploiesti
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Irkutsk
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Perm
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Banska Bystrica
country: Slovakia
city: Kosice
country: Slovakia
city: Lucenec
country: Slovakia
city: Nitra
country: Slovakia
city: Presov
country: Slovakia
city: Prievidza
country: Slovakia
city: Sahy
country: Slovakia
city: Zilina
country: Slovakia
city: Centurion
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: Kwazulu-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: Pretoria
country: South Africa
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Zaporizhzhya
country: Ukraine
Study officials:
affiliation: Takeda
name: Vice President, Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.