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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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4 January 2022 |
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Main ID: |
EUCTR2005-006029-94-CZ |
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Date of registration:
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04/03/2008 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of E5555, and its Effects on Markers of Intravascular Inflammation in Subjects with Coronary Artery Disease - E5555-G000-201
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Scientific title:
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A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of E5555, and its Effects on Markers of Intravascular Inflammation in Subjects with Coronary Artery Disease - E5555-G000-201 |
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Date of first enrolment:
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28/05/2008 |
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Target sample size:
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600 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-006029-94 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Belgium
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Czech Republic
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Germany
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Hungary
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Netherlands
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
• Age 45 – 80 years, inclusive
• Males or Females (women of child-bearing potential must use adequate protection)
• Confirmed coronary artery disease defined as one of the following:
- Post-ACS or MI or Post PCI (greater than 4 weeks) or
- CABG (greater than 12 weeks) or
- Angina pectoris with documented (ECG or imaging study) ischemia or
- Angiographically documented lesion occluding =70% of a coronary vessel
And at high risk as defined by one or more of the following:
• Screening hsCRP = 3.0 mg/L
• History of diabetes mellitus under Rx treatment
• Documented history of peripheral arterial disease
• Documented history of Thrombo-embolic TIA or stroke greater than 1 year prior to screening
• Documented history of Carotid artery disease
All subjects must be receiving low-dose (75-325 mg) aspirin and or clopidogrel 75 mg once daily. Ticlopidine 250mg twice daily with or without low dose aspirin once daily is also allowed. These medications must be taken for at least 1 month prior to screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
• Unwilling or unable to provide informed consent
•History of acquired or congenital bleeding disorder, coagulopathy, or platelet disorder
• Recent trauma or major surgery in the past 30 days prior to Screening
• Evidence of active pathological bleeding at screening or history of bleeding (such as gastrointestinal or genitourinary) within the 6 months prior to Screening, unless the cause has been definitely corrected
• History of intracranial bleeding (eg, hemorrhagic stroke, subdural hematoma, subarachnoid hemorrhage) or history of hemorrhagic retinopathy
• History of ischemic stroke or transient ischemic attack within the past year prior to Screening or known structural cerebral vascular lesion (eg, arterial venous malformation, aneurysm)
• Hematological abnormalities: INR >1.5 or PTT >1.5 X ULN, Platelet count
<100 x (10)3/µL (<100 x (10)9/L), Hemoglobin <10 g/dL at Screening
• History of New York Heart Association class 3 or 4 congestive heart failure or history of severe, uncontrolled cardiac arrhythmias at Screening
• Significant (as determined by the Investigator) cardiovascular events in the 30 days prior to the Screening Visit or newly prescribed or dose adjustments made to cardiovascular medications in the 30 days prior to the Screening Visit
• Planned elective surgical operation or major invasive procedure from 30 days before screening to completion of the study (The decision of what constitutes a major invasive procedure will be at the discretion of the investigator in conjunction with review and approval by the medical monitor)
• Unstable diabetes requiring frequent adjustments to medications (other than insulin) in the 30 days prior to the Baseline Visit
• Documented history of chronic liver disease and/or Screening ALT or AST >3 x ULN or Total Bilirubin >1.5 x ULN (unless the abnormal bilirubin level is secondary to Gilbert’s syndrome)
• Documented presence of rheumatologic or autoimmune diseases requiring continuous treatment with anti-inflammatory agents
• Significant renal impairment, defined as creatinine clearance <30 mL/min
• History of cancer (other than basal cell carcinoma of the skin, cervical carcinoma in situ, or low-grade prostate cancer), unless adequately treated with no evidence of disease recurrence for at least 2 years
• Recent (within 14 days prior to Baseline Visit) significant infection or history of chronic infections with a recurrence <14 days prior to the Screening Visit and/or requiring continuous antibiotic treatment
• Use of any of the following drugs in the 30 days prior to Screening and for the duration of the study:
- Oral anti-thrombotics other than low dose aspirin (daily aspirin dose of 325 mg
or lower) and/or clopidogrel (75 mg) and/or ticlopidine (250 mg bid)
- Anticoagulants (eg, coumadin, warfarin)
- Fibrinolytics (eg, TPA, streptokinase, urokinase)
- NSAIDs, other than occasional use
- COX-2 inhibitors, other than occasional use
- Potent CYP (global) 3A4 inhibitors
- Selected CYP 2D6 substrates
- Herbals with antiplatelet properties: Gingko biloba, Horse chestnut
(Aesculus hippocastanum)
• Use of another investigational drug within 30 days prior to the Screening Visit or use of an investigational device (eg, unapproved stent) within 12 weeks prior to the Screening Visit
• Pregnancy
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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Coronary Artery Disease
MedDRA version: 8.1
Level: PT
Classification code 10011078
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Intervention(s)
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Product Code: E5555
Pharmaceutical Form: Film-coated tablet
CAS Number: 474550-69-1
Current Sponsor code: E5555
Other descriptive name: TRIC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Product Code: E5555
Pharmaceutical Form: Film-coated tablet
CAS Number: 474550-69-1
Current Sponsor code: E5555
Other descriptive name: TRIC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Main Objective: To assess the safety and tolerability of E5555 in patients with coronary artery disease.
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Primary end point(s): The primary goal of this study is to assess the effect of E5555 on general safety and
tolerability in high risk patients with coronary artery disease especially the risk of bleeding. The primary outcome will be the proportions of subjects with CEC-adjudicated bleeds. Cross-classification tables of CEC-adjudicated major bleeds vs treatment groups will be created. Safety and tolerability will be determined by comparison of SAEs, treatment emergent AE, treatment emergent abnormal laboratory values, and ECG changes in the three treatment groups with those in the placebo group.
The secondary endpoint used to assess efficacy issues between the treatment groups will be the proportion of subjects with CEC-adjudicated MACE events.
Exploratory parameters: To determine possible anti-inflammatory effects of E5555, the inflammatory marker hsCRP will be measured at Baseline and Weeks 2, 4, 12, 16, 20, 24, and 28. Summary estimates of other biomarkers may be created to explore the efficacy differences between the treatment groups. ANOVA or ANCOVA (if necessary to adjust for Baseline) models will be used to compare the continuous biomarkers and Fischer's exact test will be used to compare the exact proportions of subject differences in the categorical biomarkers. A regression model will be created for the platelet aggregation and demographic and inflammatory biomarkers as covariates. A Bayesian model under various prior distribution assumptions may also be employed to better understand the bleeding episode profile.
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Secondary Objective: To determine the effect of E5555 on (a) the incidence of major adverse cardiovascular effects (MACE) (cardiovascular death, myocardial infarction, stroke and refractory ischemia) and b) platelet aggregation inhibition (in qualified sites in subjects willing to take part in this component of the study). The exploratory objective being pursued is to determine the effect of E5555 on the endovascular inflammatory processes that are believed to be integral to the pathogenesis of coronary artery disease. In addition, the pharmacokinetics of E5555 and its metabolites will be determined. Qualified sites will conduct comprehensive plasma sample collection for measurement of levels of E5555 and its metabolites to evaluate the relationship between E5555 pharmacokinetics and pharmacodynamics.
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Secondary ID(s)
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2005-006029-94-GB
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E5555-G000-201
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date: 28/05/2008
Contact:
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