Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients

NCT02302508 | Withdrawn Phase 4 DMC

• 1 other identifier: 14.143
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Clopidogrel efficacy appears diminished in patients with type 2 diabetes (T2D) who continue to show an increased risk of adverse cardiovascular events and mortality compared to those without T2D.The aim of the first project is to describe the pharmacokinetic (PK) profile of three antiplatelet drugs in 4 groups of patients according to their diabetic or non-diabetic status. To this end, PK profiles will be determined after a single oral dose of 300 mg clopidogrel, 60 mg prasugrel and 180 mg ticagrelor in patients (n=108); 1) with T2D and good glycemic control; 2) with T2D and poor glycemic control; 3) with insulin-treated diabetes; and 4) non-diabetic subjects.

Conditions

Diabetes

Keywords

pharmacokinetics; drug metabolism; platelet reactivity; carboxylesterase; cytochromes p450; type 2 diabetes; active metabolite

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics (AUC0-t metabolites and parent drug) of clopidogrel, prasugrel and ticagrelor.

  The association between the T2D effects on antiplatelet drug's PK (AUC0-t metabolites, AUC0-t of parent drug) will be assessed after a single oral loading dose in patients with different diabetic status.

  30 days

Secondary Outcomes (1)

• Platelet function activities

  30 days

Study Arms (4)

T2D patients with A1C ≤7.0

EXPERIMENTAL

Clopidogrel, Prasugrel, Ticagrelor A single oral dose of clopidogrel 300 mg or prasugrel 60 mg or ticagrelor 180 mg in a randomized fashion on 3 different occasions (washout period of 12 days or more)

Drug: Clopidogrel, Prasugrel, Ticagrelor

T2D patients with A1C>7.5

EXPERIMENTAL

Clopidogrel, Prasugrel, Ticagrelor A single oral dose of clopidogrel 300 mg or prasugrel 60 mg or ticagrelor 180 mg in a randomized fashion on 3 different occasions (washout period of 12 days or more)

Drug: Clopidogrel, Prasugrel, Ticagrelor

Insulino-treated

EXPERIMENTAL

Clopidogrel, Prasugrel, Ticagrelor A single oral dose of clopidogrel 300 mg or prasugrel 60 mg or ticagrelor 180 mg in a randomized fashion on 3 different occasions (washout period of 12 days or more)

Drug: Clopidogrel, Prasugrel, Ticagrelor

Non-diabetic healthy subjects

ACTIVE COMPARATOR

Clopidogrel, Prasugrel, Ticagrelor A single oral dose of clopidogrel 300 mg or prasugrel 60 mg or ticagrelor 180 mg in a randomized fashion on 3 different occasions (washout period of 12 days or more)

Drug: Clopidogrel, Prasugrel, Ticagrelor

Interventions

Clopidogrel, Prasugrel, Ticagrelor DRUG

PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents

Also known as: Plavix, Brilinta, Effient

Insulino-treated; Non-diabetic healthy subjects; T2D patients with A1C ≤7.0; T2D patients with A1C>7.5

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants will be ≥18 years old
• Non-smokers (\>3 months)
• T2D with good glycemic control A1C\<7.0
• T2D with poor glycemic control A1C \>7.5
• Insulin-treated T2D
• Non-diabetic healthy subjects

You may not qualify if:

• Subjects with estimated glomerular filtration (MDRD) \<50 mL/min/1.73m2
• ALT and AST 3 times above the upper limit of normal
• Organ transplant recipients
• Inflammatory illnesses (i.e., polyarthritis, hepatitis, cirrhosis, active infectious diseases)
• Active cancer (except non-melanoma skin cancer)
• Uncontrolled thyroid functions
• Inflammatory bowel diseases (ulcerous colitis and Crohn's disease), bariatric surgery
• Pregnancy
• History of drug or alcohol abuse
• Platelet function disorder,
• One of the following therapies : P2Y12 inhibitors, antithrombotics, antibiotics, anticoagulant, antivirals, CYP450 inducers (carbamazepine, phenobarbital, phenytoin, rifampin, St-John's worth), CYP450 inhibitors (amiodarone, fluoxetine, verapamil), immunosuppressors, INFs, or grapefruit juice (\<4 weeks) or an investigational drug
• Intolerance or hypersensitivity to antiplatelet drugs or their excipients

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Centre de Recherche du Centre Hospitalier de l'Université de Montréal: collaborator

Study Sites (1)

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X0A9, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Interventions

Clopidogrel; Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Veronique Michaud, BPharm. PhD

  Centre de recherche du Centre Hospitalier de l'université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: November 27, 2014
• Study Start: September 1, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: July 24, 2019

Record last verified: 2017-08

Locations

CA (1)