Expertise in assessing cardiovascular endpoints in clinical trials
Under the guidance of the founder Director Professor Desmond Fitzgerald (a world renowned expert in cardiovascular pharmacology and with a specialist interest in coronary thrombosis and antithrombotic therapy), Java Clinical Research Ltd’s specialist interest is in the area of both early and late stage cardiovascular studies. We have over 10 years experience in conducting cardiology trials across the entire drug development spectrum, ranging from initial studies in Phase 2 through to post-marketing trials in Phase IV.
Consequently we have developed excellent working relationships with the key Cardiologists in Ireland, a relationship which we consider critical in ensuring a thorough understanding and appreciation of the factors critical to the success of each project and essential to enable recruitment targets and timelines for studies to be achieved as specified. Indeed, Java was responsible for the complete project management and monitoring of the Phase 2 programme for a recently licensed novel renin inhibitor.
Java also has a wealth of experience conducting cardiovascular clinical trials in the following indications:
- Acute Myocardial Infarction
- Acute Coronary Syndrome
- Angina
- Hyperlipidaemia
- Coagulation Disorders
- Stent Angioplasty
- Hypertension
- Congestive Cardiac Failure
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Platelet function in clinical trials
Quality control of platelet aggregation
Platelet function studies provide vital pharmacodynamic and population response data in trials of antiplatelet and other drugs, but most trial sites are not familiar with these assays, and data quality may suffer in multicentre trials. Our various quality control services will give more reliable platelet function data:
- Deployment of an experienced study management team, ensuring that client and site personnel understand the factors critical to the success of platelet aggregation studies.
- Provision of expert training of site personnel and validation of operators before patient recruitment.
- Preparation of user-friendly site training manuals and daily checklists for platelet aggregation assay operators.
- Expert, independent review of platelet aggregation data to ensure the validity of results and to confirm uniform quality standards.
- Specification of required corrective action when quality issues are identified.
- Assay data management.
- Identification of unexpected platelet aggregation responses due to drug interactions or during shoulder periods of drug concentration.
- Provision of ongoing expert technical support by the Java Senior Scientist to site personnel.
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Tailored studies of platelet responses
We design, manage and interpret clinical trial substudies to address issues such as pharmacokinetics; pharmacodynamics and signalling; pharmacogenomics and other sources of variability. With our involvement these studies will address crucial uncertainties in areas such as safety, mechanism of action, metabolism or population variation.
- Pharmacogenomic assessment of patient responses in the study population.
- Measurements of receptor occupancy and activation (e.g. for GP IIb/IIIa antagonists), and other flow cytometry based studies of platelets.
- Tailored analysis of particular signalling pathways, including through the P2Y12 and PAR-1 receptors, to determine platelet activation status and the effect of drug treatment more accurately.
- Pharmacodynamic assessment of drug-drug interactions.
- Assessment of the effectiveness of antiplatelet therapy using an array of platelet activating agents to reflect the range of stimuli experienced by a platelet in vivo.
- Appropriate use of platelet assay systems such as the VerifyNow system from Accumetrics and the PFA-100 device from Siemens.
- Use of ‘-omic’ technologies to identify platelet responses and population variability.
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Hypertension
A key focus of our specialist work in the area of cardiovascular medicine is Hypertension. This expertise has developed through our close working relationship with the world renowned Hypertension Specialist, Professor Eoin O Brien. Through our long standing relationship with Professor O’Brien and his team at dabl® we have significant expertise in conducting clinical trials requiring 24 hour ABPM measurements.
Ambulatory Blood Pressure Monitoring
Ambulatory Blood Pressure Monitoring (ABPM) and Home Blood Pressure Monitoring (HBPM) are now increasingly used both to test anti-hypertensive drug efficacy in clinical trials and also as a cardiac safety biomarker.
Antihypertensive clinical trials using ABPM rather than traditional blood pressure monitoring yield more accurate data, allowing fewer subjects and reducing the cost of trials. Java has considerable experience in design and management of trials invovlving ABPM, while our partners dabl® are specialists in the collection, management and analysis of ABPM and HBPM clinical study data which can be tailored to suit a particular study's needs. Together we provide a complete clinical trial solution for trials using ABPM or HBPM as measures of efficacy or cardiac safety.
We consider our expertise in trials requiring 24 hour measurements a critical success factor for our clients, in particular given that the 2009 European Medicines Agency’s draft revision guideline drawn up by the Committee for Medicinal Products for Human Use (CHMP) “Guideline on Clinical Investigation of Medicinal Products in the Treatment of Hypertension” states without ambiguity that ABPM is now mandatory in all studies for the evaluation of new antihypertensive drugs.
Moreover, the US Food and Drug Administration (FDA) 2000 guidelines, which are still in draft form, also state that “The effect of the drug over the duration of the dosing interval has generally been evaluated in recent years with ABPM studies”.
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Consultancy on the assessment of cardiovascular drugs
Areas in which our consultancy services may valuable include:
- Use of clinical trial data to facilitate product differentiation.
- Strategic trial design to provide maximum information on drug responses.
- Tailoring of information to convince key opinion leaders.
Java personnel include clinicians and basic researchers with a track record in the investigation of platelet function, with particular interest in assays measuring their effectiveness in clinical settings.
We conduct research in areas such as:
- Using thromboxane to measure platelet activation in patients undergoing myocardial infarction and thrombolysis|[Pubmed]|[Pubmed]|
- The characterisation of aspirin resistance in patients with cardiovascular disease|[Pubmed]|[Pubmed]|[Pubmed]|
- Pharmacogenomic studies of variable population responses to antiplatelet drugs|[Pubmed]|[Pubmed]|
- Investigations of GPIIb/IIIa antagonists, that helped explain the limitations of oral antagonists in chronic use|[Pubmed]|[Pubmed]|
- Identifying novel mechanisms of platelet activation through the thrombin receptor PAR1| [Pubmed]|
- Pioneering gene expression analysis in platelets| [Pubmed]|
- Applying proteomics to platelets to identify risk factors for thrombosis and signals of platelet responses to drugs.
As a result, Java has great interest and experience in trials of antiplatelet drugs, and we provide particular expertise, insights from basic research and strategic advice to our clients.