E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronary Heart Disease or High Risk of Coronary Heart Disease
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E.1.1.1 | Medical condition in easily understood language |
Coronary Heart Disease or High Risk of Coronary Heart Disease
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068617 |
E.1.2 | Term | Coronary heart disease |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 |
• To evaluate the safety of MPSK3169A on top of standard-of-care (SOC) statin in patients with an low-density lipoprotein cholesterol (LDL-c) of 90−250 mg/dL and either coronary heart disease (CHD) or a CHD risk equivalent
• To evaluate the ability of MPSK3169A to reduce LDL-c on top of SOC statin therapy in patients with an LDL-c of 90−250 mg/dL and either CHD or a CHD risk equivalent |
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E.2.2 | Secondary objectives of the trial |
The PK and PD objectives for this study are as follows:
• To characterize the serum concentration of MPSK3169A over time following multiple subcutaneous (SC) doses of MPSK3169A
• To evaluate the effect of MPSK3169A on LDL-c–related biomarkers
• To characterize the relationship between MPSK3169A concentration and the effect on LDL-c and LDL-c–related biomarkers |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH MPSK3169A STUDY GC28210. Protocol GC28210 (DNA Substudy), dated 29 February 2012. |
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E.3 | Principal inclusion criteria |
• At least one of the following:
- Coronary heart disease (CHD) with a history of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), or prior coronary angiography demonstrating coronary atherosclerosis
- A CHD risk–equivalent condition, including diabetes mellitus (type 1 or 2), chronic kidney disease, prior stroke, carotid disease, peripheral arterial disease, or abdominal aortic aneurism
- ≥2 CHD risk factors (age ≥45y for men or ≥55y for women; smoking; hypertension; low HDL cholesterol; family history of premature CHD) and a high risk of a CV event based on risk estimation systems
• Use of a standard-of-care statin at a stable dose, or intolerance of statins, without use of other lipid modifying therapies
• Fasting LDL cholesterol 90–250 mg/dL on the statin regimen above |
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E.4 | Principal exclusion criteria |
• Severe congestive heart failure (NYHA Class III-IV) or left ventricular ejection fraction ≤ 35%
• Recent (within 3 months) MI, unstable angina, stroke, transient ischemic attack, CABG, PCI, hospital admission for heart failure, major surgery, uncontrolled cardiac arrhythmia (other than atrial fibrillation or flutter), or initiation of renal replacement therapy (dialysis)
• Fasting serum triglyceride level ≥400 mg/dL
• Homozygous familial hypercholesterolemia
• Poorly controlled diabetes mellitus, hypertension or thyroid disease
• Liver or muscle disease, including abnormal test results at screening
• Pregnant or lactating
The above list is not intended to contain all factors relevant to a patient’s eligibility for the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change from baseline in LDL-c concentration at Day 169 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Absolute change from baseline in LDL-c concentration for each arm at the nadir for that arm
2. Average value over time of the change in LDL-c (absolute and percent change) for each arm, up to Day 169, weighted by the number of weeks between consecutive LDL-c measurements
3. Percent change from baseline in LDL-c concentration at Day 169 and at the nadir for each arm
4. Percent and absolute change from baseline in LDL-c concentration at all other designated timepoints
5. Percent and absolute change from baseline in total cholesterol, non–HDL-c, and apolipoprotein B (ApoB) at Day 169 and at the nadir for each arm |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at the nadir for that arm
2. up to Day 169,
3. at Day 169 and at the nadir for each arm
4. at all other designated timepoints
5. at Day 169 and at the nadir for each arm |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 |
DNA Repository (sub-study) |
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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) | 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.8.2.4 | Number of treatment arms in the trial | 6 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | No |
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 |
Canada |
Czech Republic |
Germany |
Hungary |
New Zealand |
Norway |
Slovakia |
South Africa |
United States |
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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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The end of study is defined as the first day when all patients have had a study completion visit or early termination visit, or have otherwise been discontinued from the study. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |