| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Hypercholesterolemia in patients with Type II Diabetes | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10020603 | |
| 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 determine the additional LDL-C lowering achieved by switching to Ezetimibe/Simvastatin compared to doubling the dose of Atorvastatin. | |
| E.2.2 | Secondary objectives of the trial | | To determine the effect of Ezetimibe/Simvastatin (10mg/40mg, 10mg/20mg) compared to Atorvastatin 20mg on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, LDL-C/HDL-C ratio, TC/HDL-C ratio and apolipoprotein (apo) B. (2) To further evaluate safety of Ezetimibe/Simvastatin (10mg/40mg, 10mg/20mg) compared to Atorvastatin 20mg. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | a.Patient is currently treated with atorvastatin 10 mg for at least 6 weeks.
b.Patient has Diabetes Mellitus, Type II.
c.Patient has HbA1C of less than or equal to 10.0%.
d.Patient having liver transaminases (ALT, AST) less than or equal to 50% above the upper limit of normal at Visit 1, with no active liver disease, and/or creatine kinase (CK) less than or equal to 50% above the upper limit of normal.
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| E.4 | Principal exclusion criteria | a.Female patient receiving hormone therapy not on a stable dose and regimen for at least 8 weeks prior to Visit 1 or is unwilling to continue the same regimen throughout the study.
b.Patients with alcohol consumption > 14 drink per week. (A drink is: a can of beer, glass of wine, or single measure of spirits.)
c.Patients who are pregnant or lactating.
d.Patients who have been treated with any other investigational drug within 3 months of Visit 1. (If < 3 month, contact the Clinical Monitor for a case-by-case evaluation.)
e.Any condition or situation which, in the opinion of the investigator, might pose a risk to the patient or interfere with participation in the study.
PROHIBITED MEDICAL CONDITIONS:
f.Congestive heart failure defined by NYHA Class III or IV.
g.Myocardial infarction, coronary artery bypass surgery, or angioplasty within 3 months prior to Visit 1.
h.Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160 mm Hg or diastolic > 100 mm Hg at Visit 1.
i.Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e. secondary causes of hyperlipidemia) or secondary hypercholesterolemia due to hypothyroidism, (T4 < 4 g/dL) at Visit 1. Note: Patient with a history of hypothyroidism, who is on stable therapy of thyroid hormone replacement for at least 6 weeks is eligible for enrollment if TSH level is within normal limits at screening Visit 1.
j.Impaired renal function [creatinine 177 mol/L ( 2.0 mg/dL)] or nephrotic syndrome at Visit 1.
k.Disorder of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
l.Patient who is known HIV positive.
m.Cancer within the past 5 years (except for successfully treated basal and squamous cell carcinoma).
n.History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
PROHIBITED CONCOMITANT THERAPIES:
o.Medications that are potent inhibitors of CYP3A4, including cyclosporin, systemic itraconazole or ketoconazole, erythromycin, telithromycin or clarithromycin, nefazodone, protease inhibitors. In addition, patients should not take amiodarone, verapamil, or danazol. Patient is consuming > 1 quart of grapefruit juice/day.
p.Lipid-lowering agents including fish oils, Cholestin, bile-acid sequestrants, other HMG-CoA reductase inhibitors, and niacin (>200 mg/day) taken within 6 weeks and fibrates within 8 weeks prior to randomization at Visit 2 (Day 1).
q.Oral corticosteroids (unless used as replacement therapy for pituitary/adrenal disease and on a stable regimen for at least 6 weeks prior to Visit 1).
r.Patient is not stable on cardiovascular medications, such as beta-blockers, calcium-channel blockers, ACE inhibitors, nitrates, α-adrenergic blockers, thiazide diuretics or anticoagulants (i.e. warfarin), or psyllium, other fiber-based laxatives, and/or an OTC therapy known to affect serum lipid (phytosterol margarine) for at least 6-weeks. Note: Patient will be eligible to participate if on a stable medication regimen for at least 6 weeks prior to Visit 1 and agrees to remain on the same regimen throughout the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) | | 6 weeks of treatment for elevated cholesterol only | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description | | all patients receive active medication | |
| E.8.3 | The trial involves single site in the Member State concerned | Information not present in EudraCT |
| 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.8.6 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 | | Last visit of last patient is the end of 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 | |
| E.8.9.1 | In the Member State concerned days | |
