Ignite Creation Date:
2024-05-06 @ 2:47 AM
Last Modification Date:
2024-10-26 @ 11:23 AM
Study NCT ID:
NCT02126982
Status:
COMPLETED
Last Update Posted:
2023-11-28
First Post:
2014-04-28
Brief Title:
Salts of Clopidogrel Investigation to ENsure Clinical Equivalence
Sponsor:
University of Ioannina
Organization:
University of Ioannina
Study Overview
Official Title:
Comparative Study of Clinical Efficacy and Safety of Different Clopidogrel Salts in Patients With Cardiovascular Disease A Multi-center Non-interventional Clinical Trial
Status:
COMPLETED
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SCIENCE
Brief Summary:
Clopidogrel besylate CB is not differentiated relative to the orignal clopidogrel hydrogen sulfate CHS in the pharmacokinetics and in antiplatelet potency in healthy volunteers In additionCB exhibits similar pharmacodynamic properties compared to CHS in patients with a history of acute coronary syndrome ACS and in patients with ACS undergoing percutaneous coronary intervention PCI However there is a lack of data on the clinical efficacy and safety of this salt to the original salt in patients with cardiovascular disease The aim of this study is to investigate the clinical efficacy and safety of CB in relation to that of CHS in patients eligible to receive clopidogrel
Detailed Description:
It is now well documented that platelets play an important role in the pathogenesis of acute coronary syndromes This phenomenon has significantly strengthened the position of antiplatelet drugs in treatment and prevention of these syndromes In terms of administration antiplatelet drugs are divided into two categories the oral and intravenous medications Of these oral medications are the choice for long-term or prophylactic treatment of patients with acute coronary syndrome Among them is clopidogrel which together with aspirin is now the cornerstone of antiplatelet therapy Indeed clopidogrel is a widely used antiplatelet drug It is second in sales worldwide after atorvastatin and has been prescribed to more than 100 million patients worldwide Clopidogrel can be used as monotherapy or in combination with aspirin The efficacy in reducing ischemic events in patients with ACS has been shown in more than 15 major clinical studies involving more than 200000 patients These studies also proved the safety of clopidogrel to the bleeding complications only 1-2 per yearClopidogrel is a second generation thienopyridine that inhibits the binding of ADP to purinergic receptors of platelet membrane The ADP activates platelets through different receptors coupled to G-proteins The main receptor for platelet activation by ADP is P2Y12 associated with the adenyl cyclase and cause deactivation of the resulting reduction in the levels of c-AMP The identification of this receptor led to the complete elucidation of the mechanism of action of clopidogrel which proved to be an irreversible antagonist P2Y12
Clopidogrel is a prodrug that once granted is absorbed in the intestine by a process in which an important role is played by the protein carrier ABCB1MDR1 Then clopidogrel is converted in the liver to the pharmacologically active metabolite by the action of cytochrome P450 CYP450 and mainly isoform CYP2C19 and isoforms CYP3A4 CYP3A5 CYP1A2 CYP2B6 and CYP2C9 It should be noted that 85 of clopidogrel absorbed hydrolyzed by esterases in the intestinal mucosa and blood to form biologically inactive products while only 15 of the administered drug is converted to its active metabolite which is a potent irreversible selective inhibitor of receptor P2Y12 ADP resulting in the inhibition of the activation of receptor GPIIb IIIa and thereby preventing platelet aggregation
Currently clopidogrel generic forms are available in the market Indeed in 2010 and after 10 years of circulation of the original formulation clopidogrel bisulfate under the trade names Plavix or Iscover released new generic formulations of clopidogrel generic due to expiration of the period of exclusive marketing using the original formulation Main difference of generic forms of clopidogrel to the original formulation clopidogrel bisulfate is pharmacochemical recommendation salt of clopidogrel which in the case of generic formulations is benzenesulfonic besylate or hydrochloride salt Generic formulations of clopidogrel have received marketing approval from the health authorities of the European Union Bioequivalence comparative studies of clopidogrel generic formulations in healthy volunteers for generic clopidogrel bisulfate clopidogrel besylate and clopidogrel hydrochloride have proven same pharmacodynamic and pharmacokinetic profile Considering the wide variability of platelet response to clopidogrel treatment and the high incidence of atherothrombotic events in clopidogrel hyporesponsive patients studies comparing the pharmacodynamic properties of various generic clopidogrel formulations with those of original clopidogrel bisulfate in CAD patients are essential
Therefore given the numerous generic clopidogrel salts that are commercially available today it is of importance to note that any clinical data or research results arising from the use of these formulations in patients with cardiovascular disease should be related to the specific product used and not generally to the generic clopidogrel
Our group has performed two prospective pharmacodynamic studies comparing the antiplatelet effectiveness of clopidogrel besylate with that of clopidogrel bisulfate in patients with a history of an ACS and in ACS patients undergoing PCI In both studies we showed pharmacodynamic bioequivalence in all platelet function tests performed
There is a strong need of conducting further clinical studies with adequate number of patients with each clopidogrel generic formulation commercially available in order to confirm its therapeutic equivalence with the innovator product
Clopidogrel is a prodrug that once granted is absorbed in the intestine by a process in which an important role is played by the protein carrier ABCB1MDR1 Then clopidogrel is converted in the liver to the pharmacologically active metabolite by the action of cytochrome P450 CYP450 and mainly isoform CYP2C19 and isoforms CYP3A4 CYP3A5 CYP1A2 CYP2B6 and CYP2C9 It should be noted that 85 of clopidogrel absorbed hydrolyzed by esterases in the intestinal mucosa and blood to form biologically inactive products while only 15 of the administered drug is converted to its active metabolite which is a potent irreversible selective inhibitor of receptor P2Y12 ADP resulting in the inhibition of the activation of receptor GPIIb IIIa and thereby preventing platelet aggregation
Currently clopidogrel generic forms are available in the market Indeed in 2010 and after 10 years of circulation of the original formulation clopidogrel bisulfate under the trade names Plavix or Iscover released new generic formulations of clopidogrel generic due to expiration of the period of exclusive marketing using the original formulation Main difference of generic forms of clopidogrel to the original formulation clopidogrel bisulfate is pharmacochemical recommendation salt of clopidogrel which in the case of generic formulations is benzenesulfonic besylate or hydrochloride salt Generic formulations of clopidogrel have received marketing approval from the health authorities of the European Union Bioequivalence comparative studies of clopidogrel generic formulations in healthy volunteers for generic clopidogrel bisulfate clopidogrel besylate and clopidogrel hydrochloride have proven same pharmacodynamic and pharmacokinetic profile Considering the wide variability of platelet response to clopidogrel treatment and the high incidence of atherothrombotic events in clopidogrel hyporesponsive patients studies comparing the pharmacodynamic properties of various generic clopidogrel formulations with those of original clopidogrel bisulfate in CAD patients are essential
Therefore given the numerous generic clopidogrel salts that are commercially available today it is of importance to note that any clinical data or research results arising from the use of these formulations in patients with cardiovascular disease should be related to the specific product used and not generally to the generic clopidogrel
Our group has performed two prospective pharmacodynamic studies comparing the antiplatelet effectiveness of clopidogrel besylate with that of clopidogrel bisulfate in patients with a history of an ACS and in ACS patients undergoing PCI In both studies we showed pharmacodynamic bioequivalence in all platelet function tests performed
There is a strong need of conducting further clinical studies with adequate number of patients with each clopidogrel generic formulation commercially available in order to confirm its therapeutic equivalence with the innovator product
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None