DiabetesPhase 4PANDDANCT02302508
Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients
A Phase 4 study testing Clopidogrel, Prasugrel, Ticagrelor in people with Diabetes, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes
- What is being tested?
- Clopidogrel, Prasugrel, Ticagrelor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- 1 Sep 2019to Dec 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X0A9
About this study
Official title: PANDDA Study: Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients
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.
Read the 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.
- Conditions
- Diabetes
- Being tested
- Clopidogrel, Prasugrel, Ticagrelor
- Keywords
- pharmacokinetics, drug metabolism, platelet reactivity, carboxylesterase, cytochromes p450, type 2 diabetes, active metabolite
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clopidogrel, Prasugrel, TicagrelorDrug
Also called Plavix, Brilinta, Effient
PK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: 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) Receives: Drug: Clopidogrel, Prasugrel, Ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Secondary outcomes (1)
Platelet function activities
Platelet function reactivity (pharmacodynamic) will be compared between antiplatelet agents and groups of patients.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2014 (estimated)
- Study start1 Sep 2019 (estimated)
- Primary completionDec 2020 (estimated)
- Study completionDec 2021 (estimated)
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Responsible party
- Sponsor
- Investigators
- Veronique Michaud, BPharm. PhD, Principal investigator, Centre de recherche du Centre Hospitalier de l'université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02302508
- Sponsor's protocol ID
- 14.143
- Acronym
- PANDDA
- Status last verified
- Aug 2017
- First submitted
- 11 Nov 2014
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PANDDA Study: Pharmacokinetics of Antiplatelet Drugs in Diabetic pAtients
- ClinicalTrials.gov ID
- NCT02302508
- Acronym / sponsor ID
- PANDDA / 14.143
- Conditions
- Diabetes
- Keywords
- pharmacokinetics, drug metabolism, platelet reactivity, carboxylesterase, cytochromes p450, type 2 diabetes, active metabolite
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Study start
- 1 Sep 2019 (estimated)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 27 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| T2D patients with A1C ≤7.0 | Experimental | Drug: Clopidogrel, Prasugrel, TicagrelorClopidogrel, 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) |
| T2D patients with A1C>7.5 | Experimental | Drug: Clopidogrel, Prasugrel, TicagrelorClopidogrel, 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) |
| Insulino-treated | Experimental | Drug: Clopidogrel, Prasugrel, TicagrelorClopidogrel, 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) |
| Non-diabetic healthy subjects | Active comparator | Drug: Clopidogrel, Prasugrel, TicagrelorClopidogrel, 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) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clopidogrel, Prasugrel, TicagrelorAlso: Plavix, Brilinta, EffientPK and PD parameters will be compared between groups and comparison will be performed between antiplatelet agents | Drug | Insulino-treated, Non-diabetic healthy subjects, T2D patients with A1C ≤7.0, T2D patients with A1C>7.5 |
Primary outcome
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.
1 secondary outcome
Platelet function activities
Time frame: 30 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Veronique Michaud, BPharm. PhD principal investigator
Centre de recherche du Centre Hospitalier de l'université de Montréal (CHUM)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clopidogrel, Prasugrel, Ticagrelor in people with Diabetes, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics (AUC0-t metabolites and parent drug) of clopidogrel, prasugrel and ticagrelor. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2019.