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)

• ClinicalTrials.gov Identifier: NCT03794336
• Recruitment Status: Completed
• First Posted: January 7, 2019
• Last Update Posted: April 25, 2022
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: Alogliptin; Drug: Acarbose; Drug: Metformin; Drug: Aspirin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1293 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 29, 2019
• Actual Primary Completion Date: December 14, 2020
• Actual Study Completion Date: December 14, 2020

Arms and Interventions

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 Name: Nesina; Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral administration; Drug: Aspirin; Pharmaceutical form: tablet Route of administration: oral administration; Other Name: 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: Acarbose; Pharmaceutical form: tablet Route of administration: oral administration; Other Name: Glucobay; Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral administration; Drug: Aspirin; Pharmaceutical form: tablet Route of administration: oral administration; Other Name: Bayaspirin

Outcome Measures

Primary Outcome Measures :

1. Change in Hemoglobin A1c [ Time Frame: Baseline to week 16 ]
   Change from baseline in Hemoglobin A1c at the end of study (week 16) between the two drugs
2. Overall Gastrointestinal tolerability [ Time Frame: Baseline to week 16 ]
   Incidence of any gastrointestinal adverse events during the whole treatment period.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China

CHINA

China, China

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

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.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03794336
• Other Study ID Numbers: ALOGLC08867; U1111-1210-0679 ( Other Identifier: UTN )
• First Posted: January 7, 2019
• Last Update Posted: April 25, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• 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

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Aspirin; Metformin; Alogliptin; Acarbose; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors