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Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients (PANDDA)

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ClinicalTrials.gov Identifier: NCT02302508
Recruitment Status : Not yet recruiting
First Posted : November 27, 2014
Last Update Posted : January 26, 2018
Sponsor:
Collaborator:
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Information provided by (Responsible Party):
Centre hospitalier de l'Université de Montréal (CHUM)

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.

Condition or disease Intervention/treatment Phase
Diabetes Drug: Clopidogrel, Prasugrel, Ticagrelor Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: PANDDA Study: Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients
Estimated Study Start Date : September 1, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

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)
Drug: Clopidogrel, Prasugrel, Ticagrelor
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
  • Plavix
  • Brilinta
  • Effient

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)
Drug: Clopidogrel, Prasugrel, Ticagrelor
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
  • Plavix
  • Brilinta
  • Effient

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)
Drug: Clopidogrel, Prasugrel, Ticagrelor
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
  • Plavix
  • Brilinta
  • Effient

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)
Drug: Clopidogrel, Prasugrel, Ticagrelor
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
Other Names:
  • Plavix
  • Brilinta
  • Effient




Primary Outcome Measures :
  1. Pharmacokinetics (AUC0-t metabolites and parent drug) of clopidogrel, prasugrel and ticagrelor. [ Time Frame: 30 days ]
    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.


Secondary Outcome Measures :
  1. Platelet function activities [ Time Frame: 30 days ]
    Platelet function reactivity (pharmacodynamic) will be compared between antiplatelet agents and groups of patients.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02302508


Contacts
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Contact: Veronique Michaud, BPharm. PhD 5148908000 ext 15812 v.michaud@umontreal.ca
Contact: Jacques Turgeon, BPharm. PhD 5148908045 jacques.turgeon@umontreal.ca

Locations
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Canada, Quebec
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, Canada, H2X0A9
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Investigators
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Principal Investigator: Veronique Michaud, BPharm. PhD Centre de recherche du Centre Hospitalier de l'université de Montréal (CHUM)

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Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT02302508     History of Changes
Other Study ID Numbers: 14.143
First Posted: November 27, 2014    Key Record Dates
Last Update Posted: January 26, 2018
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
pharmacokinetics
drug metabolism
platelet reactivity
carboxylesterase
cytochromes p450
type 2 diabetes
active metabolite

Additional relevant MeSH terms:
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Platelet Aggregation Inhibitors
Clopidogrel
Ticagrelor
Prasugrel Hydrochloride
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs