A Randomized, Double-Blind, Active-Controlled Study of Patients With Cardiovascular Disease and Diabetes Mellitus Not Adequately Controlled With Simvastatin or Atorvastatin: Comparison of Switching to Combination Tablet Ezetimibe/Simvastatin Versus Switching to Rosuvastatin or Doubling the Statin Dose
- Conditions
- -E78 Disorders of lipoprotein metabolism and other lipidaemiasDisorders of lipoprotein metabolism and other lipidaemiasE78
- Registration Number
- PER-022-09
- Lead Sponsor
- MERCK SHARP & DOHME PERU S.R.L.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 25
• Men or women> 18 and <80 years old.
• Patients without prior treatment with statin and / or ezetimibe and whose LDL-C value prior to selection is within the range noted in Appendix 6.5. Without prior treatment, it is defined as not having been treated with a statin and / or ezetimibe during the last 6 weeks before Visit 1.
• The patient is willing to maintain the Therapeutic Lifestyle Changes of EASD or NCEP (TLC) / ADA or similar cholesterol and glucose reducing diet throughout the study.
• A potentially fertile patient agrees to abstain or use (or have his partner use) 2 acceptable contraceptive methods for the duration of the study. Acceptable contraceptive methods are: intrauterine device (IUD), diaphragm with spermicide, condom, vasectomy and hormonal contraceptives.
• The patient has type I or type 2 diabetes mellitus (DM) with symptomatic or manifested cardiovascular disease, that is, documented coronary heart disease (CHD) and / or cerebrovascular accident / temporary ischemic accident (TIA) and / or peripheral arterial disease (PVD) [Appendix 6.6].
• LDL-C level> 70 mg / dl (1.81 mmoI / L) in Visit 2 (sample collected in Visit 1).
• The patient has liver transaminases (ALT and AST) <2.0 x ULN (sample collected at Visit 1) without active liver disease at Visit 2.
• The patient presents levels of creatine kinase (CK) levels <3.0 x ULN at Visit 2 (sample collected at Visit 1).
• The patient has completed the 6-week selection / stabilization period by taking simvastatin 20 mg or atorvastatin 10 mg.
• LDL-C level> 70 mg / dl (1.81 mmoI / L) and <160 mg / dL (4.14 mmol / L) at Visit 4 (sample collected at Visit 3).
• The patient has liver transaminases (ALT and AST) <2.0 X ULN (sample collected at Visit 3) without active liver disease at Visit 4.
• The patient has creatine kinase (CK) levels <3 X ULN at Visit 4 (sample collected at Visit 3).
• The patient has triglyceride (TG) concentrations <400 mg / dL (4.52 mmol / L) at Visit 4 (sample collected at Visit 3).
• The patient has hypersensitivity or intolerance to ezetimibe, simvastatin, atorvastatin, rosuvastatin or any component of these drugs or has a history of significant myopathy or rhabdomyolysis with ezetimibe or any statin.
• The patient is Asian
• The patient routinely consumes more than 2 alcoholic beverages per day (average> 14 alcoholic beverages per week). See Section 3.2.4
• The female patient is pregnant or breastfeeding.
• The patient has been treated with another investigational drug within 30 days of Visit 1 (Week-6).
• The patient is currently taking a stable dose of a statin listed below: Rosuvastatin 5, 10, 20, 40 mg; Simvastatin 40, 80 mg; Atorvastatin 20, 40, 80 mg; Pravastatin 80 mg
• The patient has a condition or situation that, in the opinion of the researcher, could represent a risk to the patient or interfere with participation in the study.
• The patient has congestive heart failure defined by NYHA Class III or IV (New York Heart Association).
• The patient has undergone partial iliac bypass, gastric bypass or other procedure due to major intestinal malabsorption.
• The patient has uncontrolled hypertension (treated or untreated) with systolic blood pressure> 160 mmHg or diastolic> 100 mg Hg at Visit 1 (Week -6). Researchers are encouraged to maximize blood pressure control according to pre-randomization guidelines.
• The patient has an estimated glomerular filtration rate (eGRF) <30 mL / min / 1.73 m2 based on the MDRD (Diet Modification in Kidney Disease) equation of 4 variables at Visit 1 (as performed by the Central Laboratory), nephrotic syndrome or other clinically significant kidney disease in Visit 1 (Week -6).
• The patient has an endocrine or metabolic uncontrolled disease that is known to influence serum lipids and lipoproteins (ie secondary causes of hyperlipidemia, for example hyper or hypothyroidism, Cushing´s syndrome) at Visit 1 (Week -6).
• Patient with poorly controlled diabetes mellitus (HbA1c> 8.5%) or recently diagnosed (within 3 months prior to Visit 1) or any change in antidiabetic pharmacotherapy [ie changes in dosage (with the exception of ± 10 units of insulin) or the addition of a new drug] within 3 months prior to Visit 1 or patients experiencing a recent history of repeated hypoglycemia or unstable glycemic control.
• The patient has disorders of the hematological, digestive or central nervous systems including cerebrovascular and degenerative disease that could limit the evaluation or participation in the study.
• A patient known to be HIV positive (based on medical history evaluation).
• The patient has a history of malignancy <5 years before smoking informed consent, except for basal cell skin cancer or properly treated squamous cells or cervical cancer in situ (melanoma, leukemia, lymphoma and myeloproliferative disorders are excluded of any duration).
• The patient has a history of mental instability, drug / alcohol abuse within the last 5 years or an important psychiatric illness that is poorly controlled and stable with pharmacotherapy.
• The patient is currently taking drugs that are potent inhibitors of cytochrome P450 3A4 (CYP3A4) including systemic intraconazole or ketoconazole or fluconazole, erythromycin or clarithromycin or telithromycin, nefazodone and HIV protease inhibitors.
• The patient is currently taking therapies that could increase the risk of myopathy, such as: verapamil, amiodarone or
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:All lipid determinations used in the analyzes will be those obtained through the central laboratory and will be expressed in international units.<br>Measure:Percent change from baseline in LDLC at the end point<br>Timepoints:Week 6<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:All lipid determinations used in the analyzes will be those obtained through the central laboratory and will be expressed in international units.<br>Measure:Percentage change from baseline to the end point of total cholesterol (CT), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), non-HDL-C, LDL-C / HDL-C ratio, TC / HDL-C ratio, non-HDL-C / HDL-C ratio, apolipoprotein (Apo) B, Apo AI, Apo B / Apo AI ratio and high density C-reactive protein (hs-CRP).<br>Timepoints:Week 6<br>;<br>Outcome name:All lipid determinations used in the analyzes will be those obtained through the central laboratory and will be expressed in international units.<br>Measure:Percentage of patients reaching the target LDL-C level of <70 mg / dL (1.81 mmol / L) at the end point<br>Timepoints:Week 6<br>