Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients (PANDDA)
PANDDA Study: Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Clopidogrel efficacy appears diminished in patients with T2D who continue to show an increased risk of adverse cardiovascular events and mortality compared to those without T2D. To the contrary, response to prasugrel and ticagrelor appears conserved in ACS patients with diabetes. There are several mechanisms that may be contributing to the blunted response to clopidogrel but a postulated decreased concentration of clopidogrel active metabolite is worth pursuing further.
The overall objective of this proposal is to describe the pharmacokinetic profiles of three antiplatelet drugs namely, clopidogrel, prasugrel and ticagrelor in four groups of patients according to their diabetic or non-diabetic status.
Patients (n=108) will be recruited to constitute 4 groups: Group I, 27 confirmed T2D with A1C ≤7; Group II, 27 patients with poor glycemic control A1C Patients (n=108) will be recruited to constitute 4 groups: Group I, 27 confirmed T2D with A1C <7.0; Group II, 27 patients with poor glycemic control A1C >7.5; Group III, 27 patients with insulin-treated T2D; and Group IV, 27 sex-matched non-diabetic healthy subjects. Subjects with type 2 diabetes according to the Canadian Clinical Guidelines will be recruited at the CHUM outpatient clinic. After an overnight fast, participants will be admitted to the CRCHUM's Clinical Research Unit (they will not be hospitalized). A crossover randomized study design with 3 phases (washout period of 12 days between phases) will be conducted. Subjects will receive a single oral dose of clopidogrel 300 mg or prasugrel 60 mg or ticagrelor 180 mg in a randomized fashion on 3 different occasions. Serial blood samples will be drawn and urine collected over 10 hours (PK and PD analysis).
A blood sample will be taken for pharmacogenetic analyses. Additional blood samples will be collected just before the administration of antiplatelet drugs to measure fasting insulin, glycaemia levels to determine the HOMA-IR. In addition, the following covariates namely, gender, age, weight, duration of diabetes and drug profile will be also recorded.
Their regular medication will be administered 4 hours after the administration of the antiplatelet drug.
Study Type
Phase
- Phase 4
Contacts and Locations
Study Locations
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Quebec
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Montreal, Quebec, Canada, H2X0A9
- Centre Hospitalier de l'Université de Montréal (CHUM)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: T2D patients with A1C ≤7.0
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)
|
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
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Experimental: T2D patients with A1C>7.5
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)
|
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
|
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Experimental: Insulino-treated
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)
|
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
|
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Active Comparator: Non-diabetic healthy subjects
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)
|
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Pharmacokinetics (AUC0-t metabolites and parent drug) of clopidogrel, prasugrel and ticagrelor.
Time Frame: 30 days
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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.
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30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Platelet function activities
Time Frame: 30 days
|
Platelet function reactivity (pharmacodynamic) will be compared between antiplatelet agents and groups of patients.
|
30 days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Veronique Michaud, BPharm. PhD, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM)
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 14.143
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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