Safety and Efficacy Study of Alogliptin on Glycemic Control in Subjects With Type 2 Diabetes.

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of alogliptin, once daily (QD), compared to diet and exercise, sulfonylurea, metformin and a combination of sulfonylurea and metformin for treating subjects with type 2 diabetes.

Detailed Description
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Of the approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, 90% to 95% have type 2 diabetes mellitus. The prevalence of type 2 diabetes mellitus varies among racial and ethnic populations and has been shown to increase with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a disproportionate increase in the elderly population will result in a marked increase in diabetic patients, placing an ever-increasing burden on families and the health care system. In response to this problem, Takeda Global Research & Development Center, Inc. is developing SYR-322 (alogliptin), a selective, orally available inhibitor of the enzyme dipeptidyl peptidase IV. Dipeptidyl peptidase IV 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. Individuals who want to participate in this study will be required to provide written informed consent. Study participation is anticipated to be about 14 Weeks. Multiple procedures will occur at each visit which may include blood collection, urine collection, vital signs including sitting and standing blood pressure and pulse, body height and weight, physical examinations and electrocardiograms.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Comparison Study to Determine the Efficacy and Safety of SYR110322 in Patients With Type 2 Diabetes, Who Are Either Receiving No Current Treatment or Currently Treated With Diet and Exercise, Sulfonylurea, Metformin or a Combination of Sulfonylurea and Metformin

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has type 2 diabetes mellitus and were either receiving no current treatment or currently treated with a sulfonylurea, metformin, or a combination of a sulfonylurea and metformin but experiencing inadequate glycemic control. Subjects qualified as receiving no current treatment if 1 of the following conditions applied: Subject was newly diagnosed (ie, had not received any treatment). Subject was treated with diet and exercise alone for the 3 months prior to Screening Subject had received <7 continuous days of any antidiabetic therapy within the 3 months prior to Screening. Subject had a diagnosis of type 2 diabetes mellitus based on current American Diabetes Association criteria: fasting plasma glucose ≥126 mg/dL, oral glucose tolerance test at 2 hours after administration of the glucose load must have been ≥200 mg/dL, or symptoms of diabetes plus casual plasma glucose ≥200 mg/dL. Body mass index ≥23 kg/m2 and ≤40 kg/m2. Fasting C-peptide concentration ≥0.8 ng/mL. Glycosylated hemoglobin concentration between 6.8% and 11.0%. Fasting plasma glucose >126 mg/dL at Screening. No treatment within the 3 months prior to Screening with any other agents known to have effects on glucose (other than as described above, a sulfonylurea, metformin, or a combination of a sulfonylurea and metformin in subjects on antidiabetics), including but not limited to the following: Other antidiabetic agents Investigational antidiabetic agents Niacin Regular use of systemic glucocorticoids. No treatment within the 3 months prior to Screening with weight-loss drugs If taking other non-excluded medications, must have been on a stable dose of medication for at least 4 weeks. Diastolic blood pressure ≤110 mm Hg and a systolic pressure of ≤180 mm Hg. Female subjects could neither be pregnant (confirmed by laboratory testing) nor lactating, and if of childbearing potential must have been practicing adequate contraception. Able and willing to monitor their own blood glucose concentrations with a home glucose monitor. No major illness or debility that in the investigator's opinion prohibited the subject from completing the study. Hemoglobin ≥12 g/dL for males and ≥10 g/dL for females. Hepatic transaminase ≤2 x upper limit of normal. Exclusion Criteria: History of cancer, other than squamous cell or basal cell carcinoma of the skin, that had not been in full remission for at least 1 year prior to Screening. History of proteinuria >1000 mg/day on a 12- or 24-hour urine collection OR a urine albumin/creatinine ratio >1000 μg/mg at Screening. If elevated, the subject was to be rescreened within 1 week. Serum creatinine ≥2.0 mg/dL. History of proliferative diabetic retinopathy OR any history of laser-treated retinopathy. History of treated peripheral or autonomic neuropathy. History of systolic dysfunction congestive heart failure. History of myocardial infarction within 1 year prior to Screening. History of ulcerative colitis or Crohn's disease. History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus. History of a psychiatric disorder that would affect the subject's ability to participate in the study. History of anaphylactic reaction(s) to any drug. History of angioedema. History of alcohol or substance abuse within the last 2 years. History of any surgery that could potentially affect the absorption of the study drug. Receipt of any investigational drug within the preceding 30 days or a history of receipt of an investigational antidiabetic drug within the preceding 90 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alogliptin 6.25 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks<br>* Other names: SYR110322;|
| Experimental: Alogliptin 12.5 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: SYR110322;|
| Experimental: Alogliptin 25 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: SYR110322;|
| Experimental: Alogliptin 50 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: SYR110322;|
| Experimental: Alogliptin 100 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 100 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: SYR110322;|
| Placebo Comparator: Placebo QD<br> | Drug: Placebo<br>* Alogliptin placebo-matching tablets, orally, once daily for up to 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 85. | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at day 85 or final visit and glycosylated hemoglobin collected at baseline. | Baseline and Day 85. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin at Day 43. | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at day 43 and glycosylated hemoglobin collected at baseline. | Baseline and Day 43. | 
| Change From Baseline in Fasting Plasma Glucose (Day 43). | The change between the value of fasting plasma glucose collected at day 43 and fasting plasma glucose collected at baseline. | Baseline and Day 43 | 
| Change From Baseline in Fasting Plasma Glucose (Day 85). | The change between the value of fasting plasma glucose collected at day 85 or final visit and fasting plasma glucose collected at baseline. | Baseline and Day 85. | 
| Change From Baseline in Fasting Fructosamine (Day 43). | The change between the value of fasting fructosamine collected at day 43 and fasting fructosamine collected at baseline. | Baseline and Day 43. | 
| Change From Baseline in Fasting Fructosamine (Day 85). | The change between the value of fasting fructosamine collected at day 85 or final visit and fasting fructosamine collected at baseline. | Baseline and Day 85. | 
| Change From Baseline in Total Cholesterol (Day 43). | The change between the value of cholesterol collected at day 43 and cholesterol collected at baseline. | Baseline and Day 43 | 
| Change From Baseline in Total Cholesterol (Day 85). | The change between the value of cholesterol collected at day 85 or final visit and cholesterol collected at baseline. | Baseline and Day 85. | 
| Change From Baseline in High-Density Lipoprotein Cholesterol (Day 43). | The change between high-density lipoprotein cholesterol collected at day 43 and high-density lipoprotein cholesterol collected at baseline. | Baseline and Day 43. | 
| Change From Baseline in High-Density Lipoprotein Cholesterol (Day 85). | The change between high-density lipoprotein cholesterol collected at day 85 or final visit and high-density lipoprotein cholesterol collected at baseline. | Baseline and Day 85. | 
| Change From Baseline in Low-Density Lipoprotein Cholesterol (Day 43). | The change between low-density lipoprotein cholesterol collected at day 43 and low-density lipoprotein cholesterol collected at baseline. | Baseline and Day 43. | 
| Change From Baseline in Low-Density Lipoprotein Cholesterol (Day 85). | The change between low-density lipoprotein cholesterol collected at day 85 or final visit and low-density lipoprotein cholesterol collected at baseline. | Baseline and Day 85. | 
| Change From Baseline in Triglycerides (Day 43). | The change between triglycerides collected at day 43 and triglycerides collected at baseline. | Baseline and Day 43. | 
| Change From Baseline in Triglycerides (Day 85). | The change between triglycerides collected at day 85 or final visit and triglycerides collected at baseline. | Baseline and Day 85. | 
| Mean Percent Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg/dL). | The incidence of marked hyperglycemia occurring in participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during study. Overall mean obtained by weighting the hyperglycemia percent incidence values at each time point by number of days in between visits. Mean percent incidence of marked hyperglycemia at each time point is the percent of self-monitored blood glucose measurements greater than or equal to 200 mg per dL, calculated per participant and then averaged across population. | 85 Days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Drug Therapy, Diabetes Mellitus, Type II, Type 2 Diabetes Mellitus, Hyperinsulinism, Insulin Resistance