E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10047065 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the effect of VIA-2291 100mg relative to placebo on ex vivo plaque leukotriene B4 LTB4 concentrations and changes from baseline in ex vivo LTB4 synthesis in whole blood in patients with carotid artery stenosis after 12 weeks of daily dosing. |
|
E.2.2 | Secondary objectives of the trial |
Evaluate the effect of VIA-2291 100 mg relative to placebo after 12 weeks of daily dosing on a inflammatory cell composition as measured by macrophage sectional area and T-lymphocytes/mm2 in atherosclerotic carotid plaque. b change from baseline in the following specific biomarkers leukotriene E4 LTE4 urine , high sensitivity C-reactive protein hsCRP , myeloperoxidase MPO , and monocyte chemotactic protein MCP1 also known as chemotactic cytokine L2 CCL2 . |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Willing and able to provide written informed consent Males or females 30-80 years of age Female patients must be either of non-childbearing potential i.e., surgically sterilised or post menopausal 8805;12 consecutive months without menses or, must have a negative pregnancy test at screening, not be breast feeding, and must be using an acceptable method of birth control which must continue to be used throughout the study and for 2 months after the end of the patient s participation in the study Carotid stenosis between 60 and 90 and to be scheduled for CEA surgery Clinically stable at the time of randomisation One or more of the following clinical features Prior history 4 weeks of cerebrovascular accident CVA or transient ischemic attack consistent with North American Symptomatic Carotid Endarterectomy Trial NASCET criteria or prior history of amaurosis fugax occurring at any time Diabetes haemoglobin Hb A1c between 7.0 and 11 or a history of two or more fasting blood glucose levels 125 mg/dL Baseline hsCRP 2 mg/L Echolucent plaque Grey Scale Median GSM 25 on carotid ultrasound |
|
E.4 | Principal exclusion criteria |
Acute CVA within 4 weeks of enrollment Renal insufficiency defined as creatinine 1.5 x upper limit of normal ULN Any liver disease, cirrhosis, recent hepatitis, alanine aminotransferase ALT 1 x ULN i.e., above the normal range or positive screening test for hepatitis B hepatitis B surface antigen or hepatitis C by ELISA Uncontrolled diabetes mellitus within 1 month prior to study screening, defined as HbA1c 11 at screening Congestive heart failure CHF defined by the New York Heart Association as functional Class III or IV Recent acute coronary syndrome event or coronary artery bypass graft CABG surgery within 4 weeks of enrollment Atrial fibrillation Planned cardiac intervention e.g., percutaneous coronary intervention or CABG within the next 3 months Any medical condition which in the investigator s opinion could detract from the interpretation of results such as but not limited to malignant, autoimmune, chronic infections, or chronic inflammatory conditions which could affect the biomarkers used in this study Participation in any other investigational drug study within 30 days of screening History of alcohol or drug abuse per Diagnostic and Statistical Manual-IV criteria see within the past year Acetaminophen use in any form in the 7 days before enrollment |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Concentration of ex vivo plaque LTB4 and change from baseline in ex vivo LTB4 synthesis in whole blood after 12 weeks dosing. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |