Efficacy and Safety of Alogliptin vs. Acarbose in Chinese Type 2 Diabetes Mellitus (T2DM) Patients With High CV Risk or CHD Treated With Aspirin and Inadequately Controlled With Metformin Monotherapy or Drug Naive

Study Overview
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Brief Summary
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Primary Objectives: To assess efficacy in terms of change from baseline in Hemoglobin A1c (HbA1c) at the end of study between the two drugs. To assess tolerability in terms of overall Gastrointestinal (GI) tolerability for Alogliptin compared with acarbose during the whole treatment period. Secondary Objectives: To assess efficacy in terms of the percentage of patients achieving HbA1c<7%. To assess efficacy in terms of percentage of patients achieving HbA1c<7% without GI effects. To assess change from baseline in Fasting plasma glucose (FPG), 2-h Post plasma glucose (2-h PPG), β-cell function (HOMA-β), lipids and body weight. To assess safety in terms of occurrence of hypoglycemia events. To assess safety in terms of other adverse events. To assess patient adherence and tolerability.

Detailed Description
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The duration of the study for each patient will be approximately 17 weeks consisting of about 1 week screening period and 16-week treatment period.

Official Title
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Efficacy and Safety of Alogliptin vs. Acarbose in Chinese T2DM Patients With High CV Risk or CHD Treated With Aspirin and Inadequately Controlled With Metformin Monotherapy or Drug Naive: A Multicenter, Randomized, Open Label, Prospective Study

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Alogliptin
* Drug: Acarbose
* Drug: Metformin
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Type 2 Diabetes Mellitus patients (age ≥18yr) drug naive or treated with metformin monotherapy (≥1500 mg/day or individually maximally tolerated dose) for at least 12 weeks with a Hemoglobin A1c between ≥ 7.5% and ≤ 11.0% at screening. Fasting plasma glucose ≤13.3mmol/L(≤240mg/dL) at screening. Patients with documented history of Coronary Heart Disease (CHD) or High cardiovascular(CV) risk. History of CHD, defined as previous myocardial infarction or unstable/stable angina. High CV risk, defined as male or female (age> 50 yr), combined with at least one of these risk factors as below: family history of cardiovascular disease, history of hypertension, smoking, dyslipidemia, or protein urine. Already treated with Aspirin or should start Aspirin treatment at physician's discretion. Exclusion criteria: Diagnosis of type 1 diabetes, diabetes resulting from pancreatic injury or secondary forms of diabetes. Previous treatment with any Dipeptidyl Peptidase -4 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonists within 1 year of screening; Any contraindication of Aspirin, Dipeptidyl Peptidase- 4 inhibitor and Alpha-glucosidase inhibitor. Clinically apparent liver disease or moderate /severe renal impairment or end-stage renal disease Unstable CV disorder including heart failure (New York Heart Association class III or IV), refractory angina, uncontrolled arrhythmias, and severe uncontrolled hypertension (systolic blood pressure ≥180 mmHg, or diastolic blood pressure ≥105 mmHg). Acute coronary syndrome event within 6 month before randomization The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alogliptin<br>Single dose of alogliptin once daily for 16 weeks | Drug: Alogliptin<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>* Other names: Nesina;Drug: Metformin<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>Drug: Aspirin<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>* Other names: Bayaspirin;|
| Active Comparator: Acarbose<br>Thrice daily dose of acarbose Dose 1 for 7 days then titrate to thrice daily dose of of acarbose Dose 2 | Drug: Acarbose<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>* Other names: Glucobay;Drug: Metformin<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>Drug: Aspirin<br>* Pharmaceutical form: tablet Route of administration: oral administration<br>* Other names: Bayaspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin A1c | Change from baseline in Hemoglobin A1c at the end of study (week 16) between the two drugs | Baseline to week 16 | 
| Overall Gastrointestinal tolerability | Incidence of any gastrointestinal adverse events during the whole treatment period. | Baseline to week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients achieving HbA1c <7% | Percentage of patients achieving HbA1c <7% at the end of study | Baseline to Week 16 | 
| Percentage of patients achieving HbA1c <7% without gastrointestinal effects | Percentage of patients achieving HbA1c <7% without gastrointestinal effects at the end of study | Baseline to Week 16 | 
| Change in Fasting Plasma Glucose (FPG) | Change in FPG from baseline to week 16 between the two groups of drugs | Baseline to Week 16 | 
| Occurrence of hypoglycemia events | Number of patients reporting hypoglycemia events | Baseline to Week 16 | 
| Other Adverse Events (AEs) | Number of patients reporting other Adverse Events | Baseline to Week 16 | 
| Overall tolerability | Percentage of patients who discontinued study treatment as a result of adverse drug reaction | Baseline to Week 16 | 
| Change in Postprandial Plasma Glucose 2-h (PPG) | Change in PPG from baseline to week 16 between two groups of drug | Baseline to Week 16 | 
| Change in Homeostasis model assessment-β (HOMA- β) | Change in HOMA- β from baseline to week 16 between two groups of drug | Baseline to Week 16 | 
| Change in Total Cholesterol (TC) | Changes from baseline in TC to week 16 between the two groups | Baseline to Week 16 | 
| Change in Tri Glycerides (TG) | Changes from baseline in TG to week 16 between the two groups | Baseline to Week 16 | 
| Change in High Density Lipoprotein-Cholesterol (HDL-C) | Changes from baseline in HDL-C to week 16 between the two groups | Baseline to Week 16 | 
| Change in Low Density Lipoprotein-Cholesterol (LDL-C) | Changes from baseline in LDL-C to week 16 between the two groups. | Baseline to Week 16 | 
| Change in body weight | Changes from baseline in body weight to week 16 between the two groups | Baseline to Week 16 | 
| Overall adherence to Investigational Medicinal Product (IMP) | Calculated as overall dosing actually taken IMPs divided by the expected overall dosing as per protocol | Baseline to Week 16 | 
| Medication possession ratio (MPR) | Calculated as number of days actually taken IMPs divided by the expected number of days as per protocol | Baseline to Week 16 |