E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027763 |
E.1.2 | Term | Mixed hyperlipidemia |
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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 |
Main objective: In patients with mixed hyperlipidemia, to evaluate the effect of MK 0524B (dosed as MK-0524A coadministered with simvastatin) compared to atorvastatin in the percent reduction from baseline in the LDL-C/HDL-C ratio after 12 weeks of treatment for the following dose comparisons: 2g/20 mg MK-0524B vs. 10 mg atorvastatin, 2g/40 mg MK-0524B vs. 20 mg atorvastatin, 2g/40 mg MK-0524B vs. 40 mg atorvastatin, and 2g/40 mg MK-0524B vs. 80 mg atorvastatin. |
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E.2.2 | Secondary objectives of the trial |
In patients with mixed hyperlipidemia: To evaluate the effect of MK-0524B (dosed as MK-0524A coadministered with simvastatin) compared to atorvastatin: - on increasing HDL-C after 12 weeks of treatment . - on decreasing triglycerides after 12 weeks of treatment. - on decreasing non-HDL-C after 12 weeks of treatment. - on decreasing LDL-C after 12 weeks of treatment. - on Apo B, Apo A-I, lipoprotein and apolipoprotein ratios, Lp(a), and CRP after 12 weeks of treatment. To assess the safety and tolerability of MK-0524B (dosed as MK-0524A coadministered with simvastatin). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient is male or female ≥18 and ≤ 80 years of age on day of signing informed consent. Contaception for female patients who are of reproductive potential: agree to remain abstinent or use (or partner use) 2 acceptable methods of birth control for duration of study Patient meets one of the following criteria (based on NCEP ATP III categorization of CHD risk) at Visit 2 : Following Washout of Previous Lipid-Lowering Therapy Multiple Risk Patient has been washed out of a statin or other lipid-modifying therapy and has multiple risk factors (≥2 RF) with an LDL-C ≥130 mg/dL and ≤160 mg/dL (3.4 and 4.1 mmol/L). Low Risk Patient has been washed off of a statin or other lipid-modifying therapy and is low risk (0-1 RF) with an LDL-C ≥130 mg/dL and ≤190 mg/dL (3.4 and 5.0 mmol/L). Naïve patients (not currently on lipid-lowering therapy) High Risk Patient is not on a statin or other lipid-modifying therapy and is high risk (CHD/CHD risk equivalent including diabetes) with an LDL-C ≥130 mg/dL and ≤160 mg/dL (3.4 and 4.1 mmol/L). Multiple Risk Patient is not on a statin or other lipid-modifying therapy and has multiple risk factors (≥2 RF) with an LDL-C ≥130 mg/dL and ≤160 mg/dL (3.4 and 4.1 mmol/L). Low Risk Patient is not on a statin or other lipid-modifying therapy and is low risk (0-1 RF) an LDL-C ≥130 mg/dL and ≤190 mg/dL (3.4 and 5.0 mmol/L).
Triglycerides (TG) concentrations ≥150 mg/dL to ≤500 mg/dL (1.7 - 5.6 mmol/L) at Visit 2.
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E.4 | Principal exclusion criteria |
Patient has the following exclusionary laboratory values at Visit 1: • Creatinine >2.0 mg/dL (177 micromol/L) • ALT (SGPT) >1.5 x ULN • AST (SGOT) >1.5 x ULN • CK >2 x ULN • Abnormal TSH
Patient with Type 1 or Type 2 diabetes mellitus and: • is poorly controlled (HbA1C at Screening >8%) • is newly diagnosed (within 3 months of Visit 1) • is taking new or recently adjusted antidiabetic pharmacotherapy (with the exception of ± 10 units of insulin) within 3 months of Visit 2. • is taking lipid altering therapy which would require washout prior to study participation.
Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia, such as hypothyroidism or hyperthyroidism).
Patient has (as specified in the protocol): nephrotic syndrome or clinically significant renal disease, chronic heart failure, active peptic ulcer or episode of gout within 1 year of Visit 1
Patient has a history of hypersensitivity or allergic reaction to niacin or niacin-containing products, simvastatin, or atorvastatin. Patient has history of myocardial infarction, stroke, coronary artery bypass surgery or other revascularization procedure, unstable angina or angioplasty within 3 months of Visit 1.
Patient has (as specified in the protocol): uncontrolled/unstable cardiac arrhythmias/hypertension, MI, stroke, coronary bypass. Ileal/gastric bypass, chronic hepatic disease, or is HIV positive
Prohibited concomitant therapies (as specified in the protocol): patient is on potent inhibitors of CYP3A4, niacin more than 50mg/day, orlistat, sibutramine, or other anti-obesity medication, systemic corticosteroids
Patient is on lipid-modifying agents including fish oils >500 mg, bile-acid sequestrants, HMG-CoA reductase inhibitors, ezetimibe, ezetimibe/simvastatin, Cholestin™ and other red rice yeast products within 6 weeks and fibrates within 8 weeks prior to Visit 2. Patients are eligible for participation in this study ONLY after the prespecified washout period as indicated.
Patient is a woman currently taking hormonal contraceptives or intermittent use of HRTs (e.g., estradiol, medroxyprogesterone, progesterone).
Patient is taking the following antioxidant vitamins: Vitamin C in excess of 1500 mg/day Vitamin E in excess of 45 IU/day for men, 36 IU for women Beta Carotene 15000 IU for men 12000 IU/day for women
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameter is the percent change from baseline in LDL-C/HDL-C ratio following 12 weeks of active treatment. In addition, LDL-C, HDL-C, total cholesterol, triglycerides, non-HDL-C, Apo B, Apo A-1, lipoprotein and apolipoprotein ratios, Lp(a), and CRP will be assessed in all patients. |
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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 | 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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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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Date of the last visit of the last patient |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |