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 (ACADEMIC)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Alogliptin; Drug: Metformin; Drug: Aspirin; Drug: Acarbose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1293
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • China, China
    • China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Alogliptin; Single dose of alogliptin once daily for 16 weeks	Drug: Alogliptin; Pharmaceutical form: tablet Route of administration: oral administration; Other Names: Nesina; Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral administration; Drug: Aspirin; Pharmaceutical form: tablet Route of administration: oral administration; Other Names: Bayaspirin
ACTIVE_COMPARATOR: Acarbose; Thrice daily dose of acarbose Dose 1 for 7 days then titrate to thrice daily dose of of acarbose Dose 2	Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral administration; Drug: Aspirin; Pharmaceutical form: tablet Route of administration: oral administration; Other Names: Bayaspirin; Drug: Acarbose; Pharmaceutical form: tablet Route of administration: oral administration; Other Names: Glucobay

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Gao B, Gao W, Wan H, Xu F, Zhou R, Zhang X, Ji Q. Efficacy and safety of alogliptin versus acarbose in Chinese type 2 diabetes patients with high cardiovascular risk or coronary heart disease treated with aspirin and inadequately controlled with metformin monotherapy or drug-naive: A multicentre, randomized, open-label, prospective study (ACADEMIC). Diabetes Obes Metab. 2022 Jun;24(6):991-999. doi: 10.1111/dom.14661. Epub 2022 Mar 22.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 29, 2019
• Primary Completion (ACTUAL): December 14, 2020
• Study Completion (ACTUAL): December 14, 2020

Study Registration Dates

• First Submitted: January 3, 2019
• First Submitted That Met QC Criteria: January 3, 2019
• First Posted (ACTUAL): January 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Glycoside Hydrolase Inhibitors; Aspirin; Metformin; Acarbose; Alogliptin
• Other Study ID Numbers: ALOGLC08867; U1111-1210-0679 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No