Assessing Pharmacokinetics and Pharmacodynamics of Daily Enteric-coated Aspirin in Patients With StablE Diabetes II

NCT05702463 | Recruiting Phase 1

• 1 other identifier: ICM 2023-3231
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 study will include patients suffering from type 2 diabetes mellitus and will first study their response to enteric coated aspirin at a dose of 80 mg per day for a 7-day period. Participants with an incomplete platelet inhibition after exposure to EC aspirin at doses of 80 mg once daily will be randomized to a random order of 3 different ASA regimens: EC ASA 162 mg once daily, EC ASA 81 mg twice daily and chewable ASA 40 mg twice daily. The aims are to determine the feasibility of a larger scale trial, and to determine the regimen associated with the lowest proportion of non-responders after randomization. Platelet function will be assessed at baseline and at day 7 of each arms of the study.

Conditions

Type 2 Diabetes; Platelet Aggregation Inhibitors; Platelet Aggregation; Aspirin; Diabetes Mellitus, Type 2

Keywords

diabetes; aspirin; Acetylsalicylic acid; Pharmacodynamics

Outcome Measures

Primary Outcomes (5)

• Describe the screening rate to evaluate the feasibility of a larger scale randomized controlled trial.

  Determine the average number of potential participants referred to us from the Montreal Clinical Research Institute (IRCM), Centre Épic, Montreal Heart Institute and the COLCOT-T2D study who are screened per month. Hypothesis : at least 40 potential participants per month will be screened on average

  1 year

• Describe the enrollment rate by the proportion of referred participants who are eligible to evaluate the feasibility of a larger scale randomized controlled trial.

  Hypothesis : at least 70 percent of referred patients will be eligible

  1 year

• Describe the enrollment rate by the proportion of eligible participants who consent to evaluate the feasibility of a larger scale randomized controlled trial.

  Hypothesis : At least 40 percent of eligible patients will give their consent to participate in the run-in phase and the study

  1 year

• Describe the retention rate to evaluate the feasibility of a larger scale randomized controlled trial.

  Determine the retention rate of randomized participants Hypothesis : at least 85 percent of all randomized subjects will complete all study visits

  1 year

• Among initial ASA non-responder participants, define the proportion of participants that remain ASA non-responders with different formulations and dosing regimens of ASA.

  Hypothesis : in at least one of the regimens studied, the proportion of ASA non-responders will be less than 50 percent.

  1 year

Secondary Outcomes (6)

• Adherence rate to study protocol

  1 year

• Average time per participant required to complete study enrolment and all data collection.

  1 year

• Proportion of non-responders participants at day 7 of 40 mg twice daily chewable ASA regimen, 81 mg twice daily EC ASA regimen and 162 mg once daily EC ASA regimen.

  1 year

• For the run-in phase, characterize the prevalence of ASA non-responders at steady state following a 7-day treatment with ASA EC 81 mg once daily in participants with type 2 diabetes.

  1 year

• Proportion of participants who are non-responders to ASA with each dose as measured by serum levels of thromboxane B2 (TxB2).

  1 year

Study Arms (3)

EC ASA 162 mg once daily for 7 days

EXPERIMENTAL

EC ASA 162 mg once daily for 7 days

Drug: Aspirin 162 mg EC Tab once daily for 7 days

EC ASA 81 mg twice daily for 7 days

EXPERIMENTAL

EC ASA 81 mg twice daily for 7 days

Drug: Aspirin 81Mg Ec Tab twice daily for 7 days

chewable ASA 40 mg twice daily for 7 days

EXPERIMENTAL

chewable ASA 40 mg twice daily for 7 days

Drug: Aspirin 40Mg Chew Tab twice daily for 7 days

Interventions

Aspirin 81Mg Ec Tab twice daily for 7 days DRUG

Participants with incomplete platelet aggregation will be instructed to take EC ASA 81 mg twice daily for 7 days.

Also known as: ASA 81 mg EC Tab

EC ASA 81 mg twice daily for 7 days

Aspirin 40Mg Chew Tab twice daily for 7 days DRUG

Participants with incomplete platelet aggregation will be instructed to take chewable ASA 40 mg twice daily for 7 days.

Also known as: ASA 40 mg Chew Tab

chewable ASA 40 mg twice daily for 7 days

Aspirin 162 mg EC Tab once daily for 7 days DRUG

Participants with incomplete platelet aggregation will be instructed to take EC ASA 162 mg once daily for 7 days.

Also known as: ASA 162 mg EC Tab

EC ASA 162 mg once daily for 7 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• Participant must be naïve to ASA, defined as absence of chronic treatment with ASA within the previous 3 months, and of any ASA use within the previous 2 weeks;
• Type 2 diabetes, based on at least one of the following criteria: (5)
• Chronic treatment with oral antihyperglycemic agents or insulin therapy;
• Fasting Plasma Glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) (fasting is defined as no caloric intake for at least 8h);
• h Plasma Glucose (2h-PG) ≥ 200 mg/dL (11.1 mmol/L) during the oral glucose tolerance test (OGTT);
• A1C ≥ 6.5% (48 mmol/ml);
• Willing to attend all study visits of both the run-in and randomized phases of the trial.

You may not qualify if:

• Definitive indication for ASA, including any evidence of clinical atherosclerotic disease, previous or current;
• Known hypersensitivity to ASA;
• Patient requiring dialysis;
• Severe hepatic insufficiency or ALT \> 3 x ULN;
• High-risk GI bleeding features, such as known H. pylori infection, past or present ulcer, history of bleeding from the GI tract;
• Bleeding diathesis;
• Platelet count or hemoglobin levels outside of the normal reference range;
• Planned major surgical procedure or dental procedure during the course of the study;
• Chronic inflammatory disease requiring regular anti-inflammatory treatment;
• Chronic treatment with an oral anticoagulant, an antiplatelet agent, NSAIDs or systemic steroids;
• Active cancer;
• History of hematological malignancy or myelodysplasia;
• Pregnant or lactating women;

Sponsors & Collaborators

• Montreal Heart Institute: lead
• Heart and Stroke Foundation of Canada: collaborator

Study Sites (1)

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

RECRUITING

Related Publications (4)

• Marquis-Gravel G, Roe MT, Harrington RA, Munoz D, Hernandez AF, Jones WS. Revisiting the Role of Aspirin for the Primary Prevention of Cardiovascular Disease. Circulation. 2019 Sep 24;140(13):1115-1124. doi: 10.1161/CIRCULATIONAHA.119.040205. Epub 2019 Sep 23.

  PMID: 31545683 BACKGROUND

• ASCEND Study Collaborative Group; Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018 Oct 18;379(16):1529-1539. doi: 10.1056/NEJMoa1804988. Epub 2018 Aug 26.

  PMID: 30146931 BACKGROUND

• Lordkipanidze M, Pharand C, Schampaert E, Palisaitis DA, Diodati JG. Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease. Int J Cardiol. 2011 Jul 1;150(1):39-44. doi: 10.1016/j.ijcard.2010.02.025. Epub 2010 Mar 7.

  PMID: 20207433 BACKGROUND

• Bhatt DL, Grosser T, Dong JF, Logan D, Jeske W, Angiolillo DJ, Frelinger AL 3rd, Lei L, Liang J, Moore JE, Cryer B, Marathi U. Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus. J Am Coll Cardiol. 2017 Feb 14;69(6):603-612. doi: 10.1016/j.jacc.2016.11.050. Epub 2017 Jan 11.

  PMID: 28089180 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Aspirin; Mastication

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Eating; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Study Officials

• Guillaume Marquis Gravel, MD, MSc

  ICM Co. Ltd.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guillaume Marquis Gravel, MD, MSc

CONTACT

514-376-3330; guillaume.marquis.gravel@umontreal.ca

Marie Lordkipanidzé B. Pharm, Ph.D.

CONTACT

514-376-3330; marie.lordkipanidze@umontreal.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: laboratory personnel doing the platelet function assay will be blinded to minimize potential assessment bias.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: triple crossover

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: January 27, 2023
• Study Start: June 13, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)