E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
heterozygous familial hypercholesterolemia (HeFH) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057099 |
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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 |
In patients with heterozygous familial hypercholesterolemia (HeFH): (1) To demonstrate the effects of MK-0524A coadministered with intensive low-density lipoprotein cholesterol (LDL-C) lowering therapy compared to intensive LDL C lowering therapy alone on atherosclerosis progression as measured with non-invasive B-mode ultrasound carotid artery intima medial thickeness (cIMT) measurements. |
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E.2.2 | Secondary objectives of the trial |
To investigate the efficacy of MK-0524A coadministered with intensive LDL-C lowering therapy compared to intensive LDL-C lowering therapy alone on: (1) lipid profile, as assessed by LDL-C, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A-I, Apo B, lipoprotein (a) [Lp(a)], TC/ HDL-C ratio, LDL-C/HDL-C ratio, Apo B/A1 ratio, non-HDL-C; (2) high sensitivity C reactive protein (hsCRP); (3) the incidence of CV events, defined as the composite of CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, carotid revascularization, and hospitalization for unstable angina; (4) long-term safety; and (5) relationship between changes in lipoproteins and change in cIMT.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who are 18 to 70 years of age with Heterozygous Familial Hypercholesterolemia and a LDL-C greater than or equal to 100mg/dL and triglycerides less than or equal to 400 mg/dL at Visit 1 while on a stable dose of intensive LDL-C lowering therapy. |
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E.4 | Principal exclusion criteria |
A condition which, in the opinion of the investigator,might pose a risk to the patient or interfere with participating in the study, patients with <80% drug study compliance, patients with chronic medical conditions know to influence serum lipids or lipoproteins or significantly affect the ultrasound acoustic window, and patients with unstable dose of medications. Pregnant or lactating women, or women intending to become pregnant are excluded. Patient with diabetes mellitus that is poorly controlled, newly diagnosed, has recently experienced repeated hypoglycemia or unstable glycemic control, or is taking new or recently adjusted antidiabetic pharmacotherapy (with the exception of ± 10 units of insulin). Patients with the following conditions: high grade stenosis (>75%) of the carotid artery, chronic heart failure, uncontrolled/unstable cardiac arrhythmias, unstable hypertension, active or chronic hepatobiliary or hepatic disease, HIV positive, episode of gout (within 1 year). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to the end-of-treatment in the ultrasound-determined carotid artery intima medial thickeness (cIMT) (measured as the mean-Mean cIMT of the right and left common carotid artery, carotid bulb, and internal carotid arteries on a per subject basis). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Imaging Study (B-mode ultrasound) |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |