None listed
Conditions
Interventions
SCH 58235 + Placebo Type of group
SCH 58235 10 mg plus oral statin placebo for 12 days.
Group name:Placebo + simvastatin Type of group
Placebo of SCH 58235 plus simvastatin 40 mg orally for 12 days.
Sponsors
SCHERING PLOUGH RESEARCH INSTITUTE,
Eligibility
Inclusion criteria
Inclusion criteria: • Adults or children (> 12 years or> 40 kg), any sex, any race. • In all women, the result of the pregnancy test must be negative before entering the study. Women of childbearing age must agree to use an effective barrier method of contraception during the course of the study, up to one month after treatment. • Postmenopausal women receiving hormone replacement therapy or raloxifene should maintain a stable estrogen (ERT), estrogen / progestogen (HRT) or raloxifene regimen during the study period. ERT, HRT or raioxifene can not be changed during the study period. • Patients with homozygous familial hypercholesterolemia with plasma LDL cholesterol> 100 mg / dL (> 2.59 mmol / L) while being treated with atorvastatin 40 mg or simvastatin 40 mg. Familial hypercholesterolemia can be diagnosed by a.) Genetic tests or b.) If the patient has a history of LDL-C> 220 mg / dL with the maximum tolerated lipid-lowering treatment and a response <15% to that therapy in addition to LDL-C above the 90th percentile in two or more relatives of the first degree and the presence of tendinous xanthomas in the relatives and / or premature corneal arch and / or manifestations of premature coronary heart disease. • Patients must be willing to comply with the Stage I diet recommended by the NCEP or a stricter diet (NCEP Step I - see the • Appendix E) as determined by a RISCC score (Ratio of saturated fats and cholesterol ingested / calories) not greater than 24 during this study. The ability to complete the Diet Diaries must be demonstrated. • Patients must be willing to participate in the study and to comply with all follow-up evaluations. • Patients, or in the case of children, their parents or legal guardian, must agree to give written informed consent.
Exclusion criteria
Exclusion criteria: • Individuals with a history of mental instability, drug or alcohol abuse, or individuals who have been treated or are being treated for severe psychiatric conditions that, in the opinion of the investigator, may impede optimal participation in the study. • Individuals who are in a situation or have a condition that, in the opinion of the Investigator, could impede optimal participation in the study. • Underlying disease that is likely to limit life expectancy to less than 1 year. • Patients who have previously joined any of the studies that evaluate SCH 58235. • Pregnant women or those who are breastfeeding. • Known hypersensitivity or any contraindication to treatment with statins. • Concomitant diseases • Congestive heart failure Class III or IV according to NYHA. • Uncontrolled cardiac arrhythmias. • Myocardial infarction, coronary bypass or angioplasty within 3 months before entering the study. • Severe or unstable peripheral arterial disease within 3 months prior to study entry. • Unstable angina pectoris. • Disorders of the hematological, digestive, central nervous systems, including cerebrovascular disease and degenerative disease that would limit the evaluation or participation in the study. • Diabetes mellitus not controlled (as determined by HbAic) or recently diagnosed (within 1 month before admission to the study). • Endocrine or metabolic disease with known influence on serum lipids or lipoproteins. Clinically euthyroid patients who are receiving thyroid hormone replacement doses can be incorporated into the study. • Known impairment of renal function (creatinine> 2.0 mg / dL), dysproteinemia, nephrotic syndrome or other kidney disease (24-hour urinary proteins> 3+ or 1 gram). • Active or chronic hepatic or hepatobiliary disease. In addition, patients with ASI or ALT> 2 times the upper limit of the reference range of the central laboratory will be excluded. • Patients known to be HIV positive. • Patients with coagulopathy (PT or PTT at Visit 2> 1.25 times the control). • Concomitant (prohibited) medications • Derivatives of fibric acid. • Oral gorticosteroids. • Cardiovascular drugs such as; beta-blockers, calcium channel blockers, AGE inhibitors (angiotensin-converting enzyme), nitrates or α-adrenergic blockers or thiazide diuretics will be allowed as long as the dose remains constant during the course of the study and the patient has received a stable dose for eight weeks before the first determination of LDL-G performed to determine the subject´s eligibility to enter the randomization (Q1). Acetylsalicylic acid administered as an analgesic or inhibitor of platelet aggregation is allowed. • Treatment with psyllium or other fiber-based laxative unless the patient has been treated with a stable regimen for at least four weeks before the initial lipid determination to determine eligibility for randomization. The dose should be kept constant during the study period. • Treatment with orlistat. • Cyclosporine treatment. • Treatment with troglitazone (Rezulin®) or other antidiabetic agents with thiazo-linedinone unless it has been treated with a stable regimen for at least 4 weeks before the initial lipid determination to determine eligibility for randomization. The dose should be kept constant during the study period. • Use of any drug in the research phase within 30 days prior to entering the study. • Trea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The primary efficacy variable is the percentage change with respect to the Start in the direct LDL-C by ultracentrifugation at the end point of the study (last evaluation after randomization for each patient). The comparison of primary efficacy will be made between the combined group of patients receiving only statins (atorvastatin 80 mg, simvastatin 80 mg) and the combined group of patients receiving statins plus SCH 58235 10 mg (regardless of the dose of statin). The analysis will be carried out using a one-way analysis of variance model that extracts sources of variation by treatment. Measure:Efficacy Timepoints:After the treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The number of patients reporting adverse effects and the incidence of specific adverse effects will be tabulated. A list of the laboratory data will be made and the values that are outside the normal ranges will be indicated. Measure:Safety Timepoints:During and after the treatment period. | — |
Outcome results
None listed